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Routine childhood vaccinations are key for the protection of children from a variety of serious and potentially fatal diseases. Current pediatric vaccine schedules mainly cover active vaccines. Active vaccination in infants is a highly effective approach against several infectious diseases; however, thus far, for some important viral pathogens, including respiratory syncytial virus (RSV), vaccine development and license by healthcare authorities have not been accomplished. Nirsevimab is a human-derived, highly potent monoclonal antibody (mAb) with an extended half-life for RSV prophylaxis in all infants. In this manuscript, we consider the potential implications for the introduction of an anti-viral mAb, such as nirsevimab, into the routine pediatric vaccine schedule, as well as considerations for coadministration. Specifically, we present evidence on the general mechanism of action of anti-viral mAbs and experience with palivizumab, the only approved mAb for the prevention of RSV infection in preterm infants, infants with chronic lung disease of prematurity and certain infants with hemodynamically significant heart disease. Palivizumab has been used for over two decades in infants who also receive routine vaccinations without any alerts concerning the safety and efficacy of coadministration. Immunization guidelines (Advisory Committee on Immunization Practices, Joint Committee on Vaccination and Immunization, National Advisory Committee on Immunization, Centers for Disease Control and Prevention, American Academy of Pediatrics, The Association of the Scientific Medical Societies in Germany) support coadministration of palivizumab with routine pediatric vaccines, noting that immunobiologics, such as palivizumab, do not interfere with the immune response to licensed live or inactivated active vaccines. Based on the mechanism of action of the new generation of anti-viral mAbs, such as nirsevimab, which is highly specific targeting viral antigenic sites, it is unlikely that it could interfere with the immune response to other vaccines. Taken together, we anticipate that nirsevimab could be concomitantly administered to infants with routine pediatric vaccines during the same clinic visit. [ABSTRACT FROM AUTHOR]

The opinion flows from Introduction to the immunological quantum that requires a historical perspective, to Quantum vaccine algorithms supported by a bibliometric analysis, to Quantum vaccinomics describing from our perspective the different vaccinomics and quantum vaccinomics algorithms. Finally, in the Discussion and conclusions we propose novel platforms and algorithms developed to further advance on quantum vaccinomics. In the paper we refer to protective epitopes or immunological quantum for the design of candidate vaccine antigens, which may elicit a protective response through both cellular and antibody mediated mechanisms of the host immune system. Vaccines are key interventions for the prevention and control of infectious diseases affecting humans and animals worldwide. Biophysics led to quantum biology and quantum immunology reflecting quantum dynamics within living systems and their evolution. In analogy to quantum of light, immune protective epitopes were proposed as the immunological quantum. Multiple quantum vaccine algorithms were developed based on omics and other technologies. Quantum vaccinomics is the methodological approach with different platforms used for the identification and combination of immunological quantum for vaccine development. Current quantum vaccinomics platforms include in vitro , in music and in silico algorithms and top trends in biotechnology for the identification, characterization and combination of candidate protective epitopes. These platforms have been applied to different infectious diseases and in the future should target prevalent and emerging infectious diseases with novel algorithms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 de la Fuente and Contreras.)

Crimean-Congo hemorrhagic fever (CCHF) is the most prevalent tick-borne viral disease affecting humans. The disease is life-threatening in many regions of the developing world, including Africa, Asia, the Middle East, and Southern Europe. In line with the rapidly increasing disease prevalence, various vaccine strategies are under development. Despite a large number of potential vaccine candidates, there are no approved vaccines as of yet. This paper presents a detailed comparative analysis of current efforts to develop vaccines against CCHFV, limitations associated with current efforts, and future research directions. [ABSTRACT FROM AUTHOR]

Pertussis is a severe human respiratory tract infectious disease caused by Bordetella pertussis that primarily affects infants and young children. However, the acellular pertussis vaccine currently administered can induce antibody and Th2 immune responses but fails to prevent the nasal colonization and transmission of B. pertussis, causing a resurgence of pertussis, so improved pertussis vaccines are urgently needed. In this study, we created a twocomponent pertussis vaccine candidate containing a conjugate prepared from oligosaccharides and pertussis toxin. After demonstrating the ability of the vaccine to induce a mixed Th1/Th2/Th17 profile in a mouse model, the strong in vitro bactericidal activity and IgG response of the vaccine were further demonstrated. In addition, the vaccine candidate further induced efficient prophylactic effects against B. pertussis in a mouse aerosol infection model. In summary, the vaccine candidate in this paper induces antibodies with bactericidal activity to provide high protection, shorten the duration of bacterial existence, and further reduce disease outbreaks. Therefore, the vaccine has the potential to be the next generation of pertussis vaccines. [ABSTRACT FROM AUTHOR]

One of the primary tasks in vaccine design and development of immunotherapeutic drugs is to predict conformational B-cell epitopes corresponding to primary antibody binding sites within the antigen tertiary structure. To date, multiple approaches have been developed to address this issue. However, for a wide range of antigens their accuracy is limited. In this paper, we applied the transfer learning approach using pretrained deep learning models to develop a model that predicts conformational B-cell epitopes based on the primary antigen sequence and tertiary structure. A pretrained protein language model, ESM-1v, and an inverse folding model, ESM-IF1, were fine-tuned to quantitatively predict antibody-antigen interaction features and distinguish between epitope and non-epitope residues. The resulting model called SEMA demonstrated the best performance on an independent test set with ROC AUC of 0.76 compared to peer-reviewed tools. We show that SEMA can quantitatively rank the immunodominant regions within the SARS-CoV-2 RBD domain. SEMA is available at https://github.com/AIRI-Institute/SEMAi and the web-interface http://sema.airi.net., Competing Interests: Author’s DU and IL were employed by Sber. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shashkova, Umerenkov, Salnikov, Strashnov, Konstantinova, Lebed, Shcherbinin, Asatryan, Kardymon and Ivanisenko.)

Background: Recently, bacterial components were shown to enhance immune responses by shifting immune cell metabolism towards glycolysis and lactic acid production, also known as the Warburg Effect. Currently, the effect of allergen products for immunotherapy (AIT) and commercial vaccines on immune cell metabolism is mostly unknown., Objective: To investigate the effect of AIT products (adjuvanted with either MPLA or Alum) on myeloid dendritic cell (mDC) metabolism and activation., Methods: Bone marrow-derived mDCs were stimulated with five allergoid-based AIT products (one adjuvanted with MPLA, four adjuvanted with Alum) and two MPLA-adjuvanted vaccines and analyzed for their metabolic activation, expression of cell surface markers, and cytokine secretion by ELISA. mDCs were pre-incubated with either immunological or metabolic inhibitors or cultured in glucose- or glutamine-free culture media and subsequently stimulated with the MPLA-containing AIT product (AIT product 1). mDCs were co-cultured with allergen-specific CD4+ T cells to investigate the contribution of metabolic pathways to the T cell priming capacity of mDCs stimulated with AIT product 1., Results: Both the MPLA-containing AIT product 1 and commercial vaccines, but not the Alum-adjuvanted AIT products, activated Warburg metabolism and TNF-α secretion in mDCs. Further experiments focused on AIT product 1. Metabolic analysis showed that AIT product 1 increased glycolytic activity while also inducing the secretion of IL-1β, IL-10, IL-12, and TNF-α. Both rapamycin (mTOR-inhibitor) and SP600125 (SAP/JNK MAPK-inhibitor) dose-dependently suppressed the AIT product 1-induced Warburg Effect, glucose consumption, IL-10-, and TNF-α secretion. Moreover, both glucose- and glutamine deficiency suppressed secretion of all investigated cytokines (IL-1β, IL-10, and TNF-α). Glucose metabolism in mDCs was also critical for the (Th1-biased) T cell priming capacity of AIT product 1-stimulated mDCs, as inhibition of mTOR signaling abrogated their ability to induce Th1-responses., Conclusion: The AIT product and commercial vaccines containing the adjuvant MPLA were shown to modulate the induction of immune responses by changing the metabolic state of mDCs. Better understanding the mechanisms underlying the interactions between cell metabolism and immune responses will allow us to further improve vaccine development and AIT., Competing Interests: The authors are employees of the German Federal Institute for Vaccines and Biomedicines. The Paul-Ehrlich-Institut (PEI) is an Agency of the German Federal Ministry of Health. In relation to the present publication, the authors consider themselves not having a conflict of interest. Opinions expressed in the paper are personal views of the authors, not necessarily reflecting an official opinion of the PEI or the German Federal Ministry of Health., (Copyright © 2022 Zimmermann, Goretzki, Meier, Wolfheimer, Lin, Rainer, Krause, Wedel, Spies, Führer, Vieths, Scheurer and Schülke.)

Background: Candida albicans infections are particularly prevalent in immunocompromised patients. Even with appropriate treatment with current antifungal drugs, the mortality rate of invasive candidiasis remains high. Many positive results have been achieved in the current vaccine development. There are also issues such as the vaccine's protective effect is not persistent. Considering the functionality and cost of the vaccine, it is important to develop safe and efficient new vaccines with long-term effects. In this paper, an antifungal nanovaccine with Polyethyleneimine (PEI) as adjuvant was constructed, which could elicit more effective and long-term immunity via stimulating B cells to differentiate into long-lived plasma cells., Materials and Methods: Hsp90-CTD is an important target for protective antibodies during disseminated candidiasis. Hsp90-CTD was used as the antigen, then introduced SDS to "charge" the protein and added PEI to form the nanovaccine. Dynamic light scattering and transmission electron microscope were conducted to identify the size distribution, zeta potential, and morphology of nanovaccine. The antibody titers in mice immunized with the nanovaccine were measured by ELISA. The activation and maturation of long-lived plasma cells in bone marrow by nanovaccine were also investigated via flow cytometry. Finally, the kidney of mice infected with Candida albicans was stained with H&E and PAS to evaluate the protective effect of antibody in serum produced by immunized mice., Results: Nanoparticles (NP) formed by Hsp90-CTD and PEI are small, uniform, and stable. NP had an average size of 116.2 nm with a PDI of 0.13. After immunizing mice with the nanovaccine, it was found that the nano-group produced antibodies faster and for a longer time. After 12 months of immunization, mice still had high and low levels of antibodies in their bodies. Results showed that the nanovaccine could promote the differentiation of B cells into long-lived plasma cells and maintain the long-term existence of antibodies in vivo . After immunization, the antibodies in mice could protect the mice infected by C. albicans ., Conclusion: As an adjuvant, PEI can promote the differentiation of B cells into long-lived plasma cells to maintain long-term antibodies in vivo . This strategy can be adapted for the future design of vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jin, Dong, Liu, Liu, Qiu, Zhang, Zong, Hou, Guo, Sun, Chen, Dong, Li, An and Shen.)

Biomaterials hold great promise for vaccines and immunotherapy. One emerging biomaterials technology is microneedle (MNs) delivery. MNs are arrays of micrometer-sized needles that are painless and efficiently deliver cargo to the specialized immunological niche of the skin. MNs typically do not require cold storage and eliminate medical sharps. Nearly all materials exhibit intrinsic properties that can bias immune responses toward either pro-immune or inhibitory effects. Thus, because MNs are fabricated from degradable polymers to enable cargo loading and release, understanding the immunological profiles of these matrices is essential to enable new MN vaccines and immunotherapies. Additionally, understanding the mechanical properties is important because MNs must penetrate the skin and conform to a variety of skin or tissue geometries. Here we fabricated MNs from important polymer classes - including extracellular matrix biopolymers, naturally-derived polymers, and synthetic polymers - with both high- and low-molecular-weights (MW). We then characterized the mechanical properties and intrinsic immunological properties of these designs. The library of polymer MNs exhibited diverse mechanical properties, while causing only modest changes in innate signaling and antigen-specific T cell proliferation. These data help inform the selection of MN substrates based on the mechanical and immunological requirements needed for a specific vaccine or immunotherapy application., Competing Interests: CJ and RO are employees of the VA Maryland Health Care System. CJ has an equity position with Avidea Technologies. The views reported in this paper do not reflect the views of the Department of Veterans Affairs or the United States Government. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shah, Oakes, Kapnick and Jewell.)

Keywords: parasite; helminth; protozoa; Apicomplexa; flagellate; co-infection; immunity; vaccines EN parasite helminth protozoa Apicomplexa flagellate co-infection immunity vaccines 1 4 4 05/11/20 20200507 NES 200507 This Research Topic, "Immunoparasitology: A unique interplay between host and pathogen", was intended to emphasize broadly the latest advances in immunoparasitology and has been concluded with more than 30 high quality papers encompassing aspects of parasite biology, host-parasite responses and interactions, and up-to-date control measures. The author emphasizes the fact that co-infection is a common occurrence in the field, where malarial parasites, soil-transmitted helminths, bacteria and viruses, are the causes for chronic infections in a large proportion of the population. The study by Rajamanickam et al. illustrates that I Strongyloides stercoralis i infection promotes the level of eosinophil, neutrophil, and mast cell granule proteins present in peripheral blood, while anthelmintic drug treatment suppresses them, indicating a direct involvement of activated granulocytes during helminth infection. Parasite, helminth, protozoa, Apicomplexa, flagellate, co-infection, immunity, vaccines. [Extracted from the article]

Solid organ transplant recipients (SOTRs) are at increased risk for many infections, whether viral, bacterial, or fungal, due to immunosuppressive therapy to prevent organ rejection. The same immune defects that render transplanted patients susceptible to infection dampen their immune response to vaccination. Therefore, it is vital to identify immune defects to vaccination in transplant recipients and methods to obviate them. These methods can include alternative vaccine composition, dosage, adjuvants, route of administration, timing, and re-vaccination strategies. Systems biology is a relatively new field of study, which utilizes high throughput means to better understand biological systems and predict outcomes. Systems biology approaches have been used to help obtain a global picture of immune responses to infections and vaccination (i.e. systems vaccinology), but little work has been done to use systems biology to improve vaccine efficacy in immunocompromised patients, particularly SOTRs, thus far. Systems vaccinology approaches may hold key insights to vaccination in this vulnerable population., Competing Interests: NR received research funding unrelated to this paper from Sanofi-Pasteur, Pfizer, Quidel, Eli Lilly, and Merck. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Scanlon, Saklawi and Rouphael.)

The 1998 Lancet paper by Wakefield et al., despite subsequent retraction and evidence indicating no causal link between vaccinations and autism, triggered significant parental concern. The aim of this study was to analyze the online information available on this topic. Using localized versions of Google, we searched "autism vaccine" in English, French, Italian, Portuguese, Mandarin, and Arabic and analyzed 200 websites for each search engine result page (SERP). A common feature was the newsworthiness of the topic, with news outlets representing 25-50% of the SERP, followed by unaffiliated websites (blogs, social media) that represented 27-41% and included most of the vaccine-negative websites. Between 12 and 24% of websites had a negative stance on vaccines, while most websites were pro-vaccine (43-70%). However, their ranking by Google varied. While in Google.com, the first vaccine-negative website was the 43rd in the SERP, there was one vaccine-negative webpage in the top 10 websites in both the British and Australian localized versions and in French and two in Italian, Portuguese, and Mandarin, suggesting that the information quality algorithm used by Google may work better in English. Many webpages mentioned celebrities in the context of the link between vaccines and autism, with Donald Trump most frequently. Few websites (1-5%) promoted complementary and alternative medicine (CAM) but 50-100% of these were also vaccine-negative suggesting that CAM users are more exposed to vaccine-negative information. This analysis highlights the need for monitoring the web for information impacting on vaccine uptake. [ABSTRACT FROM AUTHOR]

The 16th International Symposium on Schistosomiasis, held in Brazil, focused on disease control and elimination. Participants from 11 countries discussed various aspects of schistosomiasis, including the development of disease control tools and health education. The symposium featured keynote speeches, poster presentations, panel discussions, and abstract submissions. A Research Topic dedicated to the symposium aimed to disseminate selected studies presented during the event, covering topics such as diagnostic tests, host-parasite interactions, potential drug targets, and vaccine development. These studies contribute to the search for new strategies to combat schistosomiasis. The text also highlights the importance of education and diagnostic development in achieving the World Health Organization's guidelines for controlling and eliminating the disease. [Extracted from the article]

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in young children and a substantial contributor to respiratory tract disease throughout life and as such a high priority for vaccine development. However, after nearly 60 years of research no vaccine is yet available. The challenges to developing an RSV vaccine include the young age, 2-4 months of age, for the peak of disease, the enhanced RSV disease associated with the first RSV vaccine, formalin-inactivated RSV with an alum adjuvant (FI-RSV), and difficulty achieving protection as illustrated by repeat infections with disease that occur throughout life. Understanding the biology of infection and disease pathogenesis has and will continue to guide vaccine development. In this paper, we review the roles that RSV proteins play in the biology of infection and disease pathogenesis and the corresponding contribution to live attenuated and subunit RSV vaccines. Each of RSV's 11 proteins are in the design of one or more vaccines. The G protein's contribution to disease pathogenesis through altering host immune responses as well as its role in the biology of infection suggest it can make a unique contribution to an RSV vaccine, both live attenuated and subunit vaccines. One of G's potential unique contributions to a vaccine is the potential for anti-G immunity to have an anti-inflammatory effect independent of virus replication. Though an anti-viral effect is essential to an effective RSV vaccine, it is important to remember that the goal of a vaccine is to prevent disease. Thus, other effects of the infection, such as G's alteration of the host immune response may provide opportunities to induce responses that block this effect and improve an RSV vaccine. Keeping in mind the goal of a vaccine is to prevent disease and not virus replication may help identify new strategies for other vaccine challenges, such as improving influenza vaccines and developing HIV vaccines. [ABSTRACT FROM AUTHOR]

This paper describes the sequencing protocol and computational pipeline for the PGV-001 personalized vaccine trial. PGV-001 is a therapeutic peptide vaccine targeting neoantigens identified from patient tumor samples. Peptides are selected by a computational pipeline that identifies mutations from tumor/normal exome sequencing and ranks mutant sequences by a combination of predicted Class I MHC affinity and abundance estimated from tumor RNA. The personalized genomic vaccine (PGV) pipeline is modular and consists of independently usable tools and software libraries. We hope that the functionality of these tools may extend beyond the specifics of the PGV-001 trial and enable other research groups in their own neoantigen investigations. [ABSTRACT FROM AUTHOR]

Equid alphaherpesvirus 1 (EqAHV1) is a viral pathogen known to cause respiratory disease, neurologic syndromes, and abortion storms in horses. Currently, there are no vaccines that provide complete protection against EqAHV1. Marker vaccines and the differentiation of infected and vaccinated animals (DIVA) strategy are effective for preventing and controlling outbreaks but have not been used for the prevention of EqAHV1 infection. Glycoprotein 2 (gp2), located on the envelope of viruses (EqAHV1), exhibits high antigenicity and functions as amolecular marker for DIVA. In this study, a series of EqAHV1 mutants with deletion of gp2 along with other virulence genes (TK, UL24/TK, gI/gE) were engineered. The mutant viruses were studied in vitro and then in an in vivo experiment using Golden Syrian hamsters to assess the extent of viral attenuation and the immune response elicited by the mutant viruses in comparison to the wild-type (WT) virus. Compared with the WT strain, the YM2019 Δgp2, ΔTK/gp2, and αUL24/TK/gp2 strains exhibited reduced growth in RK-13 cells, while the DgI/gE/gp2 strain exhibited significantly impaired proliferation. The YM2019 Δgp2 strain induced clinical signs and mortality in hamsters. In contrast, the YM2019 ΔTK/gp2 and αUL24/TK/gp2 variants displayed diminished pathogenicity, causing no observable clinical signs or fatalities. Immunization with nasal vaccines containing YM2019 ΔTK/gp2 and αUL24/TK/gp2 elicited a robust immune response in hamsters. In particular, compared with the vaccine containing the ΔTK/gp2 strain, the vaccine containing the αUL24/TK/gp2 strain demonstrated enhanced immune protection upon challenge with the WT virus. Furthermore, an ELISA for gp2 was established and refined to accurately differentiate between infected and vaccinated animals. These results confirm that the αUL24/TK/gp2 strain is a safe and effective live attenuated vaccine candidate for controlling EqAHV1 infection. [ABSTRACT FROM AUTHOR]

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges. [ABSTRACT FROM AUTHOR]

Introduction: Antibodies against the SARS-CoV-2 spike protein are a critical immune determinant for protection against the virus. While virus neutralization is a key function of spike-specific antibodies, antibodies also mediate Fcdependent activities that can play a role in protection or pathogenesis. Methods: This study characterized serum antibody responses elicited after two doses of heterologous adenovirus-vectored (Ad26/Ad5) vaccines. Results: Vaccine-induced antibody binding titers and Fc-mediated functions decreased over six months, while neutralization titers remained stable. Comparison of antibody isotypes elicited after Ad26/Ad5 vs. LNP-mRNA vaccination and after infection showed that anti-spike IgG1 were dominant and produced to high levels in all groups. The Ad26/Ad5 vaccines also induced IgG4 but not IgG2 and IgG3, whereas the LNP-mRNA vaccines elicited a full Ig spectrum (IgM, IgG1-4, IgA1-2). Convalescent COVID-19 patients had mainly IgM and IgA1 alongside IgG1. Despite these differences, the neutralization potencies against early variants were similar. However, both vaccine groups had antibodies with greater Fc potencies of binding complement and Fcg receptors than the COVID-19 group. The Ad26/Ad5 group also displayed a greater potency of RBD-specific antibody-mediated cellular phagocytosis. Discussion: Antibodies with distinctive quality were induced by different vaccines and infection. The data imply the utility of different vaccine platforms to elicit antibody responses with fine-tuned Fc activities. [ABSTRACT FROM AUTHOR]

This article, titled "Editorial: Women in cancer immunity and immunotherapy," discusses the contributions and challenges faced by women scientists in the field of cancer immunity and immunotherapy. It highlights the achievements of women scientists throughout history and acknowledges the gender gap that still exists in the field. The article also presents several original research articles and reviews that focus on various aspects of cancer immunity and immunotherapy. Overall, the article aims to encourage more women to pursue careers in scientific research and contribute to the advancement of the field. [Extracted from the article]

The cell-traversal protein for ookinetes and sporozoites (CelTOS), a highly conserved antigen involved in sporozoite motility, plays an important role in the traversal of host cells during the preerythrocytic stage of Plasmodium species. Recently, it has been considered an alternative target when designing novel antimalarial vaccines against Plasmodium falciparum. However, the potential of Plasmodium vivax CelTOS as a vaccine target is yet to be explored. This study evaluated the naturally acquired immune response against a recombinant P. vivax CelTOS (PvCelTOS) (IgG and IgG subclass) in 528 individuals from Brazilian Amazon, as well as the screening of B-cell epitopes in silico and peptide assays to associate the breadth of antibody responses of those individuals with exposition and/or protection correlates. We show that PvCelTOS is naturally immunogenic in Amazon inhabitants with 94 individuals (17.8%) showing specific IgG antibodies against the recombinant protein. Among responders, the IgG reactivity indexes (RIs) presented a direct correlation with the number of previous malaria episodes (p = 0.003; r = 0.315) and inverse correlation with the time elapsed from the last malaria episode (p = 0.031; r = -0.258). Interestingly, high responders to PvCelTOS (RI > 2) presented higher number of previous malaria episodes, frequency of recent malaria episodes, and ratio of cytophilic/ non-cytophilic antibodies than low responders (RI < 2) and non-responders (RI < 1). Moreover, a high prevalence of the cytophilic antibody IgG1 over all other IgG subclasses (p < 0.0001) was observed. B-cell epitope mapping revealed five immunogenic regions in PvCelTOS, but no associations between the specific IgG response to peptides and exposure/protection parameters were found. However, the epitope (PvCelTOSI136-E143) was validated as a main linear B-cell epitope, as 92% of IgG responders to PvCelTOS were also responders to this peptide sequence. This study describes for the first time the natural immunogenicity of PvCelTOS in Amazon individuals and identifies immunogenic regions in a full-length protein. The IgG magnitude was mainly composed of cytophilic antibodies (IgG1) and associated with recent malaria episodes. The data presented in this paper add further evidence to consider PvCelTOS as a vaccine candidate. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is recognized as an autoimmune joint disease driven by T cell responses to self (or modified self or microbial mimic) antigens that trigger and aggravate the inflammatory condition. Newer treatments of RA employ monoclonal antibodies or recombinant receptors against cytokines or immune cell receptors as well as small-molecule Janus kinase (JAK) inhibitors to systemically ablate the cytokine or cellular responses that fuel inflammation. Unlike these treatments, a therapeutic vaccine, such as CEL-4000, helps balance adaptive immune homeostasis by promoting antigen-specific regulatory rather than inflammatory responses, and hence modulates the immunopathological course of RA. In this review, we discuss the current and proposed therapeutic products for RA, with an emphasis on antigen-specific therapeutic vaccine approaches to the treatment of the disease. As an example, we describe published results of the beneficial effects of CEL-4000 vaccine on animal models of RA. We also make a recommendation for the design of appropriate clinical studies for these newest therapeutic approaches, using the CEL-4000 vaccine as an example. Unlike vaccines that create or boost a new immune response, the clinical success of an immunomodulatory therapeutic vaccine for RA lies in its ability to redirect autoreactive pro-inflammatory memory T cells towards rebalancing the “runaway” immune/inflammatory responses that characterize the disease. Human trials of such a therapy will require alternative approaches in clinical trial design and implementation for determining safety, toxicity, and efficacy. These approaches include adaptive design (such as the Bayesian optimal design (BOIN), currently employed in oncological clinical studies), and the use of disease-related biomarkers as indicators of treatment success. [ABSTRACT FROM AUTHOR]

Working together, two major pharmaceutical companies have developed a Lyme disease vaccine consisting of recombinant-derived outer surface protein A (OspA) of the etiologic agent Borrelia burgdorferi. Multiple clinical trials have shown the vaccine to have good safety and efficacy results, and it is hoped that it would become available for human use at least by the year 2025 after receiving approval from the U.S. Food and Drug Administration. There are still challenges left to ensure that the vaccine has, at most, minimal side effects. Also, because the previously developed Lyme disease vaccine was discontinued in 2002 after four years of distribution, due in part, for frivolous reasons having little or no scientific basis, that even led to legal entanglements involving the vaccine manufacturer and some of themedical personnel overseeing the clinical trials, there will be concerns that this newly developed one could be subject again to some of the same unnecessary scrutiny rendering its implementation suboptimal. Initially this review will focus on the key epidemiological, microbiologic, immunologic and clinical aspects of Lyme disease that provide the foundation for developing this type of vaccine that could have a serious impact on the prevalence of this and even certain other tick-transmitted infections. [ABSTRACT FROM AUTHOR]

Introduction: First described by Wallis et al. in 2001 for the assessment of TB drugs, the direct mycobacterial growth inhibition assay (MGIA) offers a tractable ex vivo tool measuring the combined influences of host immunity, strain virulence and intervention effects. Over the past 13 years, we have led efforts to adapt the direct MGIA for the assessment of TB vaccines including optimisation, harmonisation and validation of BCG vaccine-induced responses as a benchmark, as well as assay transfer to institutes worldwide. Methods: We have performed a systematic review on the primary published literature describing the development and applications of the direct MGIA from 2001 to June 2023 in accordance with the PRISMA reporting guidelines. Results: We describe 63 studies in which the direct MGIA has been applied across species for the evaluation of TB drugs and novel TB vaccine candidates, the study of clinical cohorts including those with comorbidities, and to further understanding of potential immune correlates of protection from TB. We provide a comprehensive update on progress of the assay since its conception and critically evaluate current findings and evidence supporting its utility, highlighting priorities for future directions. Discussion: While further standardisation and validation work is required, significant advancements have been made in the past two decades. The direct MGIA provides a potentially valuable tool for the early evaluation of TB drug and vaccine candidates, clinical cohorts, and immune mechanisms of mycobacterial control. [ABSTRACT FROM AUTHOR]

Coronavirus disease (Covid-19) has not only shaped awareness of the impact of infectious diseases on global health. It has also provided instructive lessons for better prevention strategies against new and current infectious diseases of major importance. Tuberculosis (TB) is a major current health threat caused by Mycobacterium tuberculosis (Mtb) which has claimed more lives than any other pathogen over the last few centuries. Hence, better intervention measures, notably novel vaccines, are urgently needed to accomplish the goal of the World Health Organization to end TB by 2030. This article describes how the research and development of TB vaccines can benefit from recent developments in the Covid-19 vaccine pipeline from research to clinical development and outlines how the field of TB research can pursue its own approaches. It begins with a brief discussion of major vaccine platforms in general terms followed by a short description of the most widely applied Covid-19 vaccines. Next, different vaccination regimes and particular hurdles for TB vaccine research and development are described. This specifically considers the complex immune mechanisms underlying protection and pathology in TB which involve innate as well as acquired immune mechanisms and strongly depend on fine tuning the response. A brief description of the TB vaccine candidates that have entered clinical trials follows. Finally, it discusses how experiences from Covid-19 vaccine research, development, and rollout can and have been applied to the TB vaccine pipeline, emphasizing similarities and dissimilarities. [ABSTRACT FROM AUTHOR]

Vaccines based on outer membrane vesicles (OMV) were developed more than 20 years ago against Neisseria meningitidis serogroup B. These nano-sized structures exhibit remarkable potential for immunomodulation of immune responses and delivery of meningococcal antigens or unrelated antigens incorporated into the vesicle structure. This paper reviews different applications in OMV Research and Development (R&D) and provides examples of OMV developed and evaluated at the Finlay Institute in Cuba. A Good Manufacturing Practice (GMP) process was developed at the Finlay Institute to produce OMV from N. meningitidis serogroup B (dOMVB) using detergent extraction. Subsequently, OMV from N. meningitidis, serogroup A (dOMVA), serogroup W (dOMVW), and serogroup X (dOMVX) were obtained using this process. More recently, the extraction process has also been applied effectively for obtaining OMV on a research scale from Vibrio cholerae (dOMVC), Bordetella pertussis (dOMVBP), Mycobacterium smegmatis (dOMVSM), and BCG (dOMVBCG). The immunogenicity of the OMV has been evaluated for specific antibody induction, and together with functional bactericidal and challenge assays in mice has shown their protective potential. dOMVB has been evaluated with non-neisserial antigens, including with a herpes virus type 2 glycoprotein, ovalbumin, and allergens. In conclusion, OMV are proving to be more versatile than first conceived and remain an important technology for development of vaccine candidates. [ABSTRACT FROM AUTHOR]

Background: Updated vaccine strategies are needed to protect against new SARS-CoV-2 variants with increased immune escape. Here, information on the safety and immunogenicity of an inactivated Omicron-adapted vaccine is presented, as compared with CoronaVac. Methods: A randomized, double-blind, active-controlled, phase III clinical trial was conducted to compare a modified Omicron-adapted vaccine (Omicron vaccine) with the authorized prototype vaccine (CoronaVac®) as a booster dose. Healthy adults aged =18 years, who have previously received 2 or 3 doses of CoronaVac (2C or 3C cohort) at least 6 months before, were enrolled to get a booster dose of Omicron vaccine or CoronaVac in a ratio of 2:1 (2C/3C+1O/1C). Back-up serums after two initial doses of CoronaVac (2C+0) for adults aged 26-45 years were collected from a previous study. Immunogenicity and safety data at 28 days after vaccination were collected and analyzed. One of the primary objectives was to evaluate the superiority of immunogenicity of Omicron vaccine booster against Omicron BA.1, compared with CoronaVac booster against BA.1. Another objective was to evaluate the non-inferiority of immunogenicity of Omicron vaccine booster against BA.1, compared with two initial doses of CoronaVac against ancestral strain. Results: Between June 1st and July 21st, 2022, a total of 1,500 healthy adults were enrolled. Results show that all pre-specified superiority criteria for BA.1 neutralizing antibody were met. Specifically, within the 3C cohort (3C+1O vs. 3C+1C), the geometric mean titers' (GMT) ratio and 95% confidence interval (CI) was 1.64 (1.42, 1.89), with the lower 95%CI =1; a GMT ratio of 1.84 (1.57, 2.16) was observed for 2C+1O versus 3C+1C. For seroconversion rate, the lower 95%CIs of differences between immuno-comparative groups (2/3C+1O vs. 3C+1C) were all above the superiority criterion 0%. However, the non-inferiority criterion of the lower 95%CI of GMT ratio =2/3 was unfulfilled for 2C/3C+1O against BA.1 versus 2C+0 against ancestral strain. Safety profiles were similar between groups, with no safety concerns identified. Conclusion: The Omicron-adapted vaccine was well-tolerated and could elicit superior immune responses as compared with CoronaVac against Omicron, while it appeared inferior to CoronaVac against ancestral strain. [ABSTRACT FROM AUTHOR]

Crimean-Congo hemorrhagic fever (CCHF) is the most prevalent tick-borne viral disease affecting humans. The disease is life-threatening in many regions of the developing world, including Africa, Asia, the Middle East, and Southern Europe. In line with the rapidly increasing disease prevalence, various vaccine strategies are under development. Despite a large number of potential vaccine candidates, there are no approved vaccines as of yet. This paper presents a detailed comparative analysis of current efforts to develop vaccines against CCHFV, limitations associated with current efforts, and future research directions.

Introduction: To control the COVID-19 pandemic, great efforts have been made to realize herd immunity by vaccination since 2020. Unfortunately, most of the vaccines against COVID-19 were approved in emergency without a full-cycle and comprehensive evaluation process as recommended to the previous vaccines. Metabolome has a close tie with the phenotype and can sensitively reflect the responses to stimuli, rendering metabolomic analysis have the potential to appraise and monitor vaccine effects authentically. Methods: In this study, a retrospective study was carried out for 330 Chinese volunteers receiving recommended two-dose CoronaVac, a vaccine approved in emergency in 2020. Venous blood was sampled before and after vaccination at 5 separate time points for all the recipients. Routine clinical laboratory analysis, metabolomic and lipidomic analysis data were collected. Results and discussion: It was found that the serum antibody-positive rate of this population was around 81.82%. Most of the laboratory parameters were slightly perturbated within the relevant reference intervals after vaccination. The metabolomic and lipidomic analyses showed that the metabolic shift after inoculation was mainly in the glycolysis, tricarboxylic acid cycle, amino acid metabolism, urea cycle, as well as microbe-related metabolism (bile acid metabolism, tryptophan metabolism and phenylalanine metabolism). Timecourse metabolome changes were found in parallel with the progress of immunity establishment and peripheral immune cell counting fluctuation, proving metabolomics analysis was an applicable solution to evaluate immune effects complementary to traditional antibody detection. Taurocholic acid, lysophosphatidylcholine 16:0 sn-1, glutamic acid, and phenylalanine were defined as valuable metabolite markers to indicate the establishment of immunity after vaccination. Integrated with the traditional laboratory analysis, this study provided a feasible metabolomics-based solution to relatively comprehensively evaluate vaccines approved under emergency. [ABSTRACT FROM AUTHOR]

Antepartum maternal vaccination can protect highly sensitive newborns before they are old enough to receive their own vaccines. Two vaccines are currently recommended during pregnancy: the flu vaccine and the Tdap vaccine against tetanus, diphtheria, and pertussis. Although there is strong evidence that maternal vaccination works to protect the offspring, limitations in the understanding of vaccines and of maternal transfer of immunity compound to obscure our understanding of how they work. Here we focus on the example of pertussis to explore the possible mechanisms involved in the transfer of protection to offspring and how these may impact the newborn's response to future exposure to pertussis. For example, Tdap vaccines induce pathogen specific antibodies, and those antibodies are known to be transferred from mother to the fetus in utero and to the newborn via milk. But antibodies alone have modest impact on pertussis disease, and even less effect on colonization/transmission. Maternal immune cells can also be transferred to offspring and may play a direct role in protection from disease and/or influence the developing neonatal immune system. However, some of the transferred immunity may also blunt the offspring's response to subsequent vaccination. In this review we will summarize the protection conferred to offspring by maternal vaccination against pertussis and the likely mechanisms by which protection is transferred, identifying the many knowledge gaps that limit our most effective application of this approach. [ABSTRACT FROM AUTHOR]

Soil-transmitted helminths affect approximately 1.5 billion people worldwide. However, as no vaccine is currently available for humans, the current strategy for elimination as a public health problem relies on preventive chemotherapy. Despite more than 20 years of intense research effort, the development of human helminth vaccines (HHVs) has not yet come to fruition. Current vaccine development focuses on peptide antigens that trigger strong humoral immunity, with the goal of generating neutralizing antibodies against key parasite molecules. Notably, this approach aims to reduce the pathology of infection, not worm burden, with only partial protection observed in laboratory models. In addition to the typical translational hurdles that vaccines struggle to overcome, HHVs face several challenges (1): helminth infections have been associated with poor vaccine responses in endemic countries, probably due to the strong immunomodulation caused by these parasites, and (2) the target population displays pre-existing type 2 immune responses to helminth products, increasing the likelihood of adverse events such as allergy or anaphylaxis. We argue that such traditional vaccines are unlikely to be successful on their own and that, based on laboratory models, mucosal and cellular-based vaccines could be a way to move forward in the fight against helminth infection. Here, we review the evidence for the role of innate immune cells, specifically the myeloid compartment, in controlling helminth infections. We explore how the parasite may reprogram myeloid cells to avoid killing, notably using excretory/secretory (ES) proteins and extracellular vesicles (EVs). Finally, learning from the field of tuberculosis, we will discuss how anti-helminth innate memory could be harnessed in a mucosal-trained immunity-based vaccine. [ABSTRACT FROM AUTHOR]

Introduction: Influenza (flu) vaccination prevented over 100,000 hospitalizations and 7000 deaths from flu over the 2019-2020 season in the USA. Infants <6 months are the most likely to die fromflu, though flu vaccines are only licensed for infants >6 months old. Therefore, it is recommended that flu vaccination occur during pregnancy, as this reduces severe complications; however, vaccination rates are suboptimal, and vaccination is also recommended postpartum. For breast/chest-fed infants, the vaccine is believed to elicit protective and robust seasonally-specificmilk antibody (Ab). Fewcomprehensive studies exist examining Ab responses in milk after vaccination, with none measuring secretory Ab (sAb). Determining whether sAbs are elicited is critical, as this Ab class is highly stable in milk and mucosae. Methods: In the present study, our aim was to determine to what extent specific Ab titers in the milk of lactating people were boosted after seasonal influenza vaccination. Over the 2019-2020 and 2020-2021 seasons, milk was obtained pre- and post-vaccination and assessed for specific IgA, IgG, and sAb against relevant hemagglutinin (HA) antigens by a Luminex immunoassay. Results: IgA and sAb were not found to be significantly boosted, while only IgG titers against B/Phuket/3073/2013, included in vaccines since 2015, exhibited an increase. Across the 7 immunogens examined, as many as 54% of samples exhibited no sAb boost. No significant differences for IgA, sAb, or IgG boosting were measured between seasonally-matched versus mismatched milk groups, indicating boosting was not seasonally-specific. No correlations between IgA and sAb increases were found for 6/8 HA antigens. No boost in IgG-or IgAmediated neutralization post vaccination was observed. Discussion: This study highlights the critical need to redesign influenza vaccines with the lactating population in mind, wherein the aim should be to elicit a potent seasonally-specific sAb response in milk. As such, this population must be included in clinical studies. [ABSTRACT FROM AUTHOR]

Immunogenicity continues to pose a challenge in the development of biotherapeutics like conventional therapeutic-proteins and monoclonal antibodies as well as emerging modalities such as gene-therapy components, gene editing, and CAR T cells. The approval of any therapeutic is based on a benefit-risk evaluation. Most biotherapeutics address serious medical conditions where the standard of care has a poor outcome. Consequently, even if immunogenicity limits the utility of the therapeutic in a sub-set of patients, the benefit-risk assessment skews in favor of approval. Some cases resulted in the discontinuation of biotherapeutics due to immunogenicity during drug development processes, This special issue presents a platform for review articles offering a critical assessment of accumulated knowledge as well as novel findings related to nonclinical risks that extend our understanding of the immunogenicity of biotherapeutics. Some of the studies in this collection leveraged assays and methodologies refined over decades to support more clinically relevant biological samples. Others have applied rapidly advancing methodologies in pathway-specific analyses to immunogenicity. Similarly, the reviews address urgent issues such as the rapidly emerging cell and gene therapies which hold immense promise but could have limited reach as a significant number of the patient population could potentially not benefit due to immunogenicity. In addition to summarizing the work presented in this special issue we have endeavored to identify areas where additional studies are required to understand the risks of immunogenicity and develop appropriate mitigation strategies. [ABSTRACT FROM AUTHOR]

Glycan masking is a novel technique in reverse vaccinology in which sugar chains (glycans) are added on the surface of immunogen candidates to hide regions of low interest and thus focus the immune system on highly therapeutic epitopes. This shielding strategy is inspired by viruses such as influenza and HIV, which are able to escape the immune system by incorporating additional glycosylation and preventing the binding of therapeutic antibodies. Interestingly, the glycan masking technique is mainly used in vaccine design to fight the same viruses that naturally use glycans to evade the immune system. In this review we report the major successes obtained with the glycan masking technique in epitopefocused vaccine design. We focus on the choice of the target antigen, the strategy for immunogen design and the relevance of the carrier vector to induce a strong immune response. Moreover, we will elucidate the different applications that can be accomplished with glycan masking, such as shifting the immune response from hyper-variable epitopes to more conserved ones, focusing the response on known therapeutic epitopes, broadening the response to different viral strains/sub-types and altering the antigen immunogenicity to elicit higher or lower immune response, as desired. [ABSTRACT FROM AUTHOR]

A defined immune profile that predicts protection against a pathogen-ofinterest, is referred to as a correlate of protection (CoP). A validated SARSCoV-2 CoP has yet to be defined, however considerable insights have been provided by pre-clinical vaccine and animal rechallenge studies which have fewer associated limitations than equivalent studies in human vaccinees or convalescents, respectively. This literature review focuses on the advantages of the use of animal models for the definition of CoPs, with particular attention on their application in the search for SARS-CoV-2 CoPs. We address the conditions and interventions required for the identification and validation of a CoP, which are often only made possible with the use of appropriate in vivo models. [ABSTRACT FROM AUTHOR]

Background: After exposure to SARS-CoV-2 and/or vaccination there is an increase in serum antibody titers followed by a non-linear waning. Our aim was to find out if this waning of antibody titers would fit to a mathematical model. Methods: We analyzed anti-RBD (receptor binding domain) IgG antibody titers and the breakthrough infections over a ten-month period following the second dose of the mRNA BNT162b2 (Pfizer-BioNtech.) vaccine, in a cohort of 54 health-care workers (HCWs) who were either never infected with SARS-CoV-2 (naïve, nHCW group, n=27) or previously infected with the virus (experienced, eHCW group, n=27). Two mathematical models, exponential and power law, were used to quantify antibody waning kinetics, and we compared the relative quality of the goodness of fit to the data between both models was compared using the Akaik Information Criterion. Results: We found that the waning slopes were significantly more pronounced for the naïve when compared to the experienced HCWs in exponential (p-value: 1.801E-9) and power law (p-value: 9.399E-13) models. The waning of anti-RBD IgG antibody levels fitted significantly to both exponential (average-R2: 0.957 for nHCW and 0.954 for eHCW) and power law (average-R2: 0.991 for nHCW and 0.988 for eHCW) models, with a better fit to the power law model. In the nHCW group, titers would descend below an arbitrary 1000-units threshold at a median of 210.6 days (IQ range: 74.2). For the eHCW group, the same risk threshold would be reached at 440.0 days (IQ range: 135.2) post-vaccination.Conclusion: Two parsimonious models can explain the anti-RBD IgG antibody titer waning after vaccination. Regardless of the model used, eHCWs have lower waning slopes and longer persistence of antibody titers than nHCWs. Consequently, personalized vaccination booster schedules should be implemented according to the individual persistence of antibody levels. [ABSTRACT FROM AUTHOR]

Nanoparticle vaccines usually prime stronger immune responses than soluble antigens. Within this class of subunit vaccines, the recent development of computationally designed self-assembling two-component protein nanoparticle scaffolds provides a powerful and versatile platform for displaying multiple copies of one or more antigens. Here we report the generation of three different nanoparticle immunogens displaying 60 copies of p67C, an 80 amino acid polypeptide from a candidate vaccine antigen of Theileria parva, and their immunogenicity in cattle. p67C is a truncation of p67, the major surface protein of the sporozoite stage of T. parva, an apicomplexan parasite that causes anoftenfatal bovine disease called East Coast fever (ECF) in sub-Saharan Africa. Compared to I32-19 and I32-28, we found that I53-50 nanoparticle scaffolds displaying p67C had the best biophysical characteristics. p67C-I53-50 also outperformed the other two nanoparticles in stimulating p67C-specific IgG1 and IgG2 antibodies and CD4+ T-cell responses, as well as sporozoite neutralizing capacity. In experimental cattle vaccine trials, p67C-I53-50 induced significant immunity to ECF, suggesting that the I53-50 scaffold is a promising candidate for developing novel nanoparticle vaccines. To our knowledge this is the first application of computationally designed nanoparticles to the development of livestock vaccines. [ABSTRACT FROM AUTHOR]

Owing to the success of linear mRNA coronavirus disease 2019 (COVID-19) vaccines, biopharmaceutical companies and research teams worldwide have attempted to develop more stable circular RNA (circRNA) vaccines and have achieved some preliminary results. This review aims to summarize key findings and important progress made in circRNA research, the in vivo metabolism and biological functions of circRNAs, and research progress and production process of circRNA vaccines. Further, considerations regarding the quality control of circRNA vaccines are highlighted herein, and the main challenges and problem-solving strategies in circRNA vaccine development and quality control are outlined to provide a reference for circRNA vaccinerelated research. [ABSTRACT FROM AUTHOR]

The emergence of Sin Nombre orthohantavirus, an etiological agent of hantavirus cardiopulmonary syndrome, exacerbates the situation and imposes a heavy financial burden on healthcare organizations. Multidrugresistant forms of the disease are prevalent, and there is currently no licensed commercial vaccine. Due to the numerous limitations of experimental vaccines, vaccines against various bacterial and viral diseases have developed via computational vaccine design. Several subtractive proteomics, immunoinformatics, docking, and simulation approaches were used in this study to develop a multi-epitope-based vaccine against Sin Nombre orthohantavirus. One possible antigenic protein--the glycoprotein precursor of surface glycoproteins (accession number >AAC42202.1)--was selected as a candidate for B cell-derived T cell epitopes mapping the detailed analysis of the core genome. Among the predicted epitopes, four epitopes (QVDWTKKSST, GLAASPPHL, SSYSYRRKLV, and MESGWSDTA), which were probably antigenic, nonallergenic, nontoxic, and water soluble, were used in the multi-epitope vaccine's construction. The shortlisted epitopes have the potency to cover 99.78% of the world's population, 97.93% of the Chinese population, and 97.36% of the Indian population. The epitopes were connected through AAY linkers and joined with >50S ribosomal adjuvant to enhance their efficacy. The vaccine comprises 182 amino acids with a molecular weight of 19.03770 kDa and an instability index of 26.52, indicating that the protein is stable. A molecular docking study revealed that the vaccine has a good binding affinity with TLR-4 and TLR-8, which is vital for inducing the immune system. Top-1 docked complexes of vaccine-TLR-4 and TLR-8 with the lowest binding energy of -12.52 kc/mol and -5.42 kc/mol, respectively, were considered for molecular dynamic simulation analysis. Furthermore, we predicted that the docked complexes are properly stable throughout simulation time in both normal mode and AMBER-based simulation analysis. The MMGBSA analysis calculated -122.17 and -125.4 net binding energies for the TLR-8- and TLR4- vaccine complexes, respectively, while the MMPBSA analysis estimated -115.63 and -118.19 for the TLR-8- and TLR4-vaccine complex, respectively, confirming that the binding stability with receptors is stable, which is important for inducing a strong response. However, the current work is computation-based, so experimental validation is highly recommended. [ABSTRACT FROM AUTHOR]

Highly mutable infectious disease pathogens (hm-IDPs) such as HIV and influenza evolve faster than the human immune system can contain them, allowing them to circumvent traditional vaccination approaches and causing over one million deaths annually. Agent-based models can be used to simulate the complex interactions that occur between immune cells and hm-IDP-like proteins (antigens) during affinity maturation--the process by which antibodies evolve. Compared to existing experimental approaches, agent-based models offer a safe, low-cost, and rapid route to study the immune response to vaccines spanning a wide range of design variables. However, the highly stochastic nature of affinity maturation and vast sequence space of hm-IDPs render brute force searches intractable for exploring all pertinent vaccine design variables and the subset of immunization protocols encompassed therein. To address this challenge, we employed deep reinforcement learning to drive a recently developed agent-based model of affinity maturation to focus sampling on immunization protocols with greater potential to improve the chosen metrics of protection, namely the broadly neutralizing antibody (bnAb) titers or fraction of bnAbs produced. Using this approach, we were able to coarse-grain a wide range of vaccine design variables and explore the relevant design space. Our work offers new testable insights into how vaccines should be formulated to maximize protective immune responses to hm-IDPs and how they can be minimally tailored to account for major sources of heterogeneity in human immune responses and various socioeconomic factors. Our results indicate that the first 3 to 5 immunizations, depending on the metric of protection, should be specially tailored to achieve a robust protective immune response, but that beyond this point further immunizations require only subtle changes in formulation to sustain a durable bnAb response. [ABSTRACT FROM AUTHOR]

We performed a review study according to recent COVID-19 vaccines’ realworld data to provide comparisons between COVID-19 vaccines regarding their relative efficacy. Although most vaccine platforms showed comparable effectiveness and efficacy, we highlight critical points and recent developments generated in studies that might affect vaccine efficacy including populationdependent effects of the vaccine (transplantation, adiposity, and specific comorbidities, as well as older age, male sex, ethnicity, and prior infection), vaccine type, variants of concern (VOC), and an extended vaccine schedule. Owing to these factors, community-based trials can be of great importance in determining vaccine effectiveness in a systematic manner; thus, uncertainty remains regarding vaccine efficacy. Long immune protection of vaccination with BNT162b2 or ChAdOx1 nCoV-19 has been demonstrated to be up to 61 months and 5–12 months after the previous infection, and boosting infectionacquired immunity for both the first and second doses of the BNT162b2 and ChAdOx1 nCoV-19 vaccines was correlated with high and durable protection. However, large cohort and longitudinal studies are required for the evaluation of immunity dynamics and longevity in unvaccinated, vaccinated, and infected individuals, as well as vaccinated convalescent individuals in real-world settings. Regarding the likelihood of vaccine escape variants evolving, an ongoing examination of the protection conferred against an evolving virus (new variant) by an extended schedule can be crucial. [ABSTRACT FROM AUTHOR]

Background: Even after complete surgical treatment or chemotherapy, Non-Small Cell Lung Cancer (NSCLC) patients are also at substantial risk for recurrence and spread trend. Therapeutic cancer vaccination could increase the anti-tumor immune response and prevent tumor relapse. This study aimed to assess the characteristics of NSCLC therapeutic vaccines registered on ClinicalTrials.gov. Methods: We conducted a cross-sectional, descriptive study of clinical trials for Non-Small Cell Lung Cancer Therapeutic Vaccines Registered on ClinicalTrials. gov (https://clinicaltrials.gov/) through March 17, 2022. Results: This study encompassed 117 registered trials included for data analysis. The number of trials was significantly correlated with a beginning year (r = 0.504, P < 0.010). Of these trials, 45.30% were completed, 12.82% were terminated, and 8.55% were withdrawn. More than half of trials (52.99%) were funded by industry, and more than half of trials (52.14%) were located in economically developed North America. Regarding study designs of these trials, 27.35% were randomized, 52.14% were single group assignment, 83.76% were without masking, 35.90% were phase 1, and more than half of the trials (56.41%) recruited less than 50 participants. The highest proportion of vaccine types was protein/peptide vaccines (41.88%). Regarding TNM staging, the highest proportion of the trials is stage III-IV (26.50%). Conclusion: The number of clinical trials about the cancer therapeutic vaccines was sustained an increase in recent years. Themain characteristic of clinical trials for NSCLC therapeutic vaccines is lack of randomized control, lack of mask, and recruiting less than 50 participants. In recent years, the protein/peptide vaccines for NSCLC active immunotherapy have been well studied. [ABSTRACT FROM AUTHOR]

Currently, vaccines for SARS-CoV-2 and influenza viruses are updated if the new vaccine induces higher antibody-titers to circulating variants than current vaccines. This approach does not account for complex dynamics of how prior immunity skews recall responses to the updated vaccine. We: (i) use computational models to mechanistically dissect how prior immunity influences recall responses; (ii) explore how this affects the rules for evaluating and deploying updated vaccines; and (iii) apply this to SARS-CoV- 2. Our analysis of existing data suggests that there is a strong benefit to updating the current SARS-CoV-2 vaccines to match the currently circulating variants. We propose a general two-dose strategy for determining if vaccines need updating as well as for vaccinating high-risk individuals. Finally, we directly validate our model by reanalysis of earlier human H5N1 influenza vaccine studies. [ABSTRACT FROM AUTHOR]

After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVCCOV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics. [ABSTRACT FROM AUTHOR]

We systematically reviewed and summarized studies focusing on Bharat Biotech's Whole Virion Inactivated Corona Virus Antigen BBV152 (Covaxin), which is India's indigenous response to fighting the SARS-CoV-2 pandemic. Studies were searched for data on the efficacy, immunogenicity, and safety profile of BBV152. All relevant studies published up to March 22, 2022, were screened from major databases, and 25 studies were eventually inducted into the systematic review. The studies focused on the virus antigen (6 μg) adjuvanted with aluminium hydroxide gel and/or Imidazo quinolin gallamide (IMDG), aTLR7/8 agonist. Pre-clinical, phase I, and II clinical trials showed appreciable immunogenicity. Both neutralizing and binding antibody titers were significant and T cell responses were Th1-biased. Phase III trials on the 6 μg +Algel-IMDG formulation showed a 93.4% efficacy against severe COVID-19. Data from the trials revealed an acceptable safety profile withmostlymild-moderate local and systemic adverse events. No serious adverse events or fatalities were seen, and most studies reportedmilder and lesser adverse events with Covaxin when compared with other vaccines, especially Oxford-Astra Zeneca's AZD1222 (Covishield). The immunogenicity performance of Covaxin, which provided significant protection only after the second dose, was mediocre and it was consistently surpassed by Covishield. One study reported adjusted effectiveness against symptomatic infection to be just 50% at 2 weeks after the second dose. Nonetheless, appreciable results were seen in previously infected individuals administered both doses. There was some evidence of coverage against the Alpha, Beta, and Delta variants. However, neither Covaxin nor Covishield showed sufficient protection against the Omicron variant. Two studies reported super-additive results on mixing Covaxin with Covishield. Further exploration of heterologous prime-boost vaccination with a combination of an inactivated vaccine and an adenoviral vector-based vaccine for tackling future variants may be beneficial. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Immunology titled "Mucosal vaccines for the induction of antimicrobial immunoglobulin A." The author discusses the importance of mucosal vaccines in inducing immunoglobulin A (IgA) antibodies, which play a crucial role in mucosal immunity. Unlike monomeric IgA found in serum, the intestinal environment contains dimeric or tetrameric forms of IgA known as secreted IgA (SIgA). Recent research has shown that mucosal IgA antibodies can effectively respond to a wide range of variants, including the SARS-CoV2 virus. The document emphasizes the need for further research to strengthen mucosal immunity and combat future pandemics. [Extracted from the article]

Clostridium difficile (C.difficile) is an exclusively anaerobic, spore-forming, and Grampositive pathogen that is the most common cause of nosocomial diarrhea and is becoming increasingly prevalent in the community. Because C. difficile is strictly anaerobic, spores that can survive for months in the external environment contribute to the persistence and diffusion of C. difficile within the healthcare environment and community. Antimicrobial therapy disrupts the natural intestinal flora, allowing spores to develop into propagules that colonize the colon and produce toxins, thus leading to antibiotic-associated diarrhea and pseudomembranous enteritis. However, there is no licensed vaccine to prevent Clostridium difficile infection (CDI). In this study, a multiepitope vaccine was designed using modern computer methods. Two target proteins, CdeC, affecting spore germination, and fliD, affecting propagule colonization, were chosen to construct the vaccine so that it could simultaneously induce the immune response against two different forms (spore and propagule) of C. difficile. We obtained the protein sequences from the National Center for Biotechnology Information (NCBI) database. After the layers of filtration, 5 cytotoxic T-cell lymphocyte (CTL) epitopes, 5 helper T lymphocyte (HTL) epitopes, and 7 B-cell linear epitopes were finally selected for vaccine construction. Then, to enhance the immunogenicity of the designed vaccine, an adjuvant was added to construct the vaccine. The Prabi and RaptorX servers were used to predict the vaccine's two- and three-dimensional (3D) structures, respectively. Additionally, we refined and validated the structures of the vaccine construct. Molecular docking and molecular dynamics (MD) simulation were performed to check the interaction model of the vaccine--Toll-like receptor (TLR) complexes, vaccine--major histocompatibility complex (MHC) complexes, and vaccine--B-cell receptor (BCR) complex. Furthermore, immune stimulation, population coverage, and in silico molecular cloning were also conducted. The foregoing findings suggest that the final formulated vaccine is promising against the pathogen, but more researchers are needed to verify it. [ABSTRACT FROM AUTHOR]

Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-fold reduction in 50% neutralizing antibody titres (NT50) against Delta and VIC31 at 6 months compared to 2 weeks after the second dose; followed by 25-fold increase at 2 weeks after the third dose. Neutralisation of Omicron was only consistently observed 2 weeks after the third dose, with most samples having titres below the limit of detection at earlier timepoints. Moderna results were similar to Pfizer at 2 weeks after the second dose, while the titres for AstraZeneca samples derived from older donors were 7-fold lower against VIC31 and below the limit of detection against Delta and Omicron. Age and gender were not found to significantly impact our results. These findings indicate that vaccine matching may be needed, and that at least a third dose of these vaccines is necessary to generate sufficient neutralising antibodies against emerging variants of concern, especially Omicron, amidst the challenges of ensuring vaccine equity worldwide. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs), the strongest antigen-presenting cells, are a focus for orchestrating the immune system in the fight against cancer. Basic scientific investigations elucidating the cellular biology of the DCs have resulted in new strategies in this fight, including cancer vaccinology, combination therapy, and adoptive cellular therapy. Although immunotherapy is currently becoming an unprecedented bench-to-bedside success, the overall response rate to the current immunotherapy in patients with gastrointestinal (GI) cancers is pretty low. Here, we have carried out a literature search of the studies of DCs in the treatment of GI cancer patients. We provide the advances in DC-based immunotherapy and highlight the clinical trials that indicate the therapeutic efficacies and toxicities related with each vaccine. Moreover, we also offer the yet-to-be-addressed questions about DC-based immunotherapy. This study focuses predominantly on the data derived from human studies to help understand the involvement of DCs in patients with GI cancers. [ABSTRACT FROM AUTHOR]

The new WHO Roadmap for Neglected Tropical Diseases targets the global elimination of schistosomiasis as a public health problem. To date, control strategies have focused on effective diagnostics, mass drug administration, complementary and integrative public health interventions. Non-mammalian intermediate hosts and other vertebrates promote transmission of schistosomiasis and have been utilized as experimental model systems. Experimental animal models that recapitulate schistosomiasis immunology, disease progression, and pathology observed in humans are important in testing and validation of control interventions. We discuss the pivotal value of these models in contributing to elimination of schistosomiasis. Treatment of schistosomiasis relies heavily on mass drug administration of praziquantel whose efficacy is comprised due to re-infections and experimental systems have revealed the inability to kill juvenile schistosomes. In terms of diagnosis, nonhuman primate models have demonstrated the low sensitivity of the gold standard Kato Katz smear technique. Antibody assays are valuable tools for evaluating efficacy of candidate vaccines, and sera from graded infection experiments are useful for evaluating diagnostic sensitivity of different targets. Lastly, the presence of Schistosomes can compromise the efficacy of vaccines to other infectious diseases and its elimination will benefit control programs of the other diseases. As the focus moves towards schistosomiasis elimination, it will be critical to integrate treatment, diagnostics, novel research tools such as sequencing, improved understanding of disease pathogenesis and utilization of experimental models to assist with evaluating performance of new approaches. [ABSTRACT FROM AUTHOR]