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The optimal immune response eliminates invading pathogens, restoring immune equilibrium without inflicting undue harm to the host. However, when a cascade of immunological reactions is triggered, the immune response can sometimes go into overdrive, potentially leading to harmful long-term effects or even death. The immune system is triggered mostly by infections, allergens, or medical interventions such as vaccination. This review examines how these immune triggers differ and why certain infections may dysregulate immune homeostasis, leading to inflammatory or allergic pathology and exacerbation of pre-existing conditions. However, many vaccines generate an optimal immune response and protect against the consequences of pathogen-induced immunological aggressiveness, and from a small number of unrelated pathogens and autoimmune diseases. Here, we propose an "immuno-wave" model describing a vaccine-induced "Goldilocks immunity", which leaves fine imprints of both pro-inflammatory and anti-inflammatory milieus, derived from both the innate and the adaptive arms of the immune system, in the body. The resulting balanced, 'quiet alert' state of the immune system may provide a jump-start in the defense against pathogens and any associated pathological inflammatory or allergic responses, allowing vaccines to go above and beyond their call of duty. In closing, we recommend formally investigating and reaping many of the secondary benefits of vaccines with appropriate clinical studies. [ABSTRACT FROM AUTHOR]

Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Conversely, the anionic adjuvant (L3) increased the cDC2 population percentage with significantly higher MHCII and DEC205 expression, along with an increase in the CD4T and regulatory T cell populations. The L3-treated group also exhibited higher percentages of activated B and plasma cell populations with significantly higher antigen-specific IgG and IgA titer and virus neutralization potential. While the anionic adjuvant induced significantly higher humoral responses than the cationic adjuvant, the latter influenced a significantly higher Th1/Th17 response. For customized vaccine development, it is beneficial to have alternative adjuvants that can generate differential immune responses with the same vaccine candidate antigen. This study will aid the selection of adjuvants based on their charges to improve specific immune response arms in the future development of vaccine formulation. [ABSTRACT FROM AUTHOR]

When the Mpox virus (MPXV) began spreading globally in 2022, it became critical to evaluate whether residual immunity from smallpox vaccination provided cross-protection. To assess the cross-immune response to MPXV, we collected serum samples (n = 97) and PBMCs (n = 30) from healthy-donors, either born before 1974 and reporting smallpox vaccination during childhood or born after 1975 and not vaccinated with Vaccinia virus (VACV)-based vaccines. We evaluated the levels of anti-MPXV IgG and neutralizing antibodies (Nabs) and the presence of a T cell response against MPXV. We found anti-MPXV IgG and Nabs in 60 (89.6%) and 40 (70.1%) vaccinated individuals, respectively. We observed a T cell response to Orthopoxviruses and MPXV peptide pools in 30% of vaccinated individuals. We thus show that a high proportion of subjects who received the smallpox vaccine 40 to 60 years ago have humoral cross-immunity, while the T-cell-specific response against MPXV was observed in a smaller group (30%) of vaccinated individuals. This study, combined with information on immunity developed during natural infection or the administration of current vaccines, will contribute to a better understanding of humoral and cellular responses against MPXV. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are indispensable for the activation, maintenance and halting of immune responses. TLRs can mediate inflammation by recognizing molecular patterns in microbes (pathogen-associated molecular patterns: PAMPs) and endogenous ligands (danger-associated molecular patterns: DAMPs) released by injured or dead cells. For this reason, TLR ligands have attracted much attention in recent years in many cancer vaccines, alone or in combination with immunotherapy, chemotherapy and radiotherapy (RT). TLRs have been shown to play controversial roles in cancer, depending on various factors that can mediate tumor progression or apoptosis. Several TLR agonists have reached clinical trials and are being evaluated in combination with standard of care therapies, including RT. Despite their prolific and central role in mediating immune responses, the role of TLRs in cancer, particularly in response to radiation, remains poorly understood. Radiation is recognized as either a direct stimulant of TLR pathways, or indirectly through the damage it causes to target cells that subsequently activate TLRs. These effects can mediate pro-tumoral and anti-tumoral effects depending on various factors such as radiation dose and fractionation, as well as host genomic features. In this review, we examine how TLR signaling affects tumor response to RT, and we provide a framework for the design of TLR-based therapies with RT. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected over 600 million individuals and caused nearly 7 million deaths worldwide (10 January 2023). Patients with renal disease undergoing hemodialysis are among those most adversely affected, with an increased predisposition to SARS-CoV-2 infection and death. This systematic review aimed to pool evidence assessing the humoral response of hemodialysis patients (HDP) post-mRNA SARS-CoV-2 vaccination. A systematic search of the literature was performed through MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers up to 10 January 2023. Cohort and case-control studies were included if they reported an immune response in one group of patients undergoing hemodialysis who received mRNA SARS-CoV-2 vaccination compared with another group of patients receiving the same vaccine but not on hemodialysis. The methodological quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was not deemed appropriate due to the high heterogeneity between studies. From the 120 studies identified, nine (n = 1969 participants) met the inclusion criteria. Most studies (n = 8/9, 88%) were of high or medium methodological quality (≥6/9 stars). The results revealed that HDP developed lower antibody levels across all timepoints post-vaccination when compared with controls. Patients with chronic kidney disease elicited the highest antibody immune response, followed by HDP and, lastly, kidney transplant recipients. Overall, post-vaccination antibody titers were comparatively lower than in the healthy population. Current results imply that robust vaccination strategies are needed to address waning immune responses in vulnerable populations. [ABSTRACT FROM AUTHOR]

Vaccines have proven to be the most cost-efficient and reasonable way to fight and exterminate virulent pathogens. Vaccines can be designed using a variety of platforms including inactivated/attenuated pathogen or subunits of it. The most recent COVID mRNA vaccines have employed nucleic acid sequences for the antigen of interest to combat the pandemic. Different vaccine platforms have been chosen for different licensed vaccines which all have shown their ability to induce durable immune responses and protection. In addition to platforms, different adjuvants have been used to strengthen the immunogenicity of vaccines. Among the delivery routes, intramuscular injection has been the most common for vaccination. In this review, we present a historical overview of the integrated consideration of vaccine platforms, adjuvants, and delivery routes in the success of vaccine development. We also discuss the advantages and limitations of each choice in the efficacy of vaccine development. [ABSTRACT FROM AUTHOR]

The avian influenza A virus (AIV) is naturally prevalent in aquatic birds, infecting different avian species and transmitting from birds to humans. Both AIVs, the H5N1 and H7N9 viruses, have the potential to infect humans, causing an acute influenza disease syndrome in humans, and are a possible pandemic threat. AIV H5N1 is highly pathogenic, whereas AIV H7N9 has comparatively low pathogenicity. A clear insight into the disease pathogenesis is significant to understand the host's immunological response, which in turn facilitates the design of the control and prevention strategies. In this review, we aim to provide comprehensive details on the pathogenesis and clinical features of the disease. Moreover, the innate and adaptive immunological responses to AIV and the recent studies conducted on the CD8+ T cell immunity against AIVs are detailed upon. Further, the current status and advancement in the development of AIV vaccines, along with the challenges, are also discussed. The information provided will be helpful in combating the transmission of AIV from birds to humans and, thus, preventing severe outbreaks leading to pandemics worldwide. [ABSTRACT FROM AUTHOR]

In the present study, antibody and T cell-mediated immune responses elicited by BBIBP-CorV and BNT162b2 vaccines were compared 6 months after the two-dose immunization of healthy individuals. Additionally, antibody and T cell responses after the third dose of BBIBP-CorV or BNT162b2 were compared using a homologous or heterologous vaccination strategy. The third dose was consistently administered 6 months after the second dose. Six months following the two-dose vaccination, the cumulative IFNγ-positive T cell response was almost identical in participants immunized with either two doses of BNT162b2 or BBIBP-CorV vaccines; however, significant differences were revealed regarding humoral immunity: the two-dose BNT162b2 vaccine maintained a significantly higher antireceptor-binding domain (RBD) IgG, anti-spike (S1/S2) IgG, and IgA antibody levels. The BNT162b2 + BNT162b2 + BBIBP-CorV vaccine series elicited significantly lower anti-RBD IgG and anti-S1/S2 IgG levels than three doses of BNT162b2, while the anti-S IgA level was equally negligible in both groups. Importantly, the cumulative IFNγ-positive T cell response was highly similar in both groups. Surprisingly, the BBIBP-CorV + BBIBP-CorV + BNT162b2 vaccination series provided a much higher cumulative IFNγ-positive T cell response than that elicited by three doses of BNT162b2; moreover, the levels of anti-RBD IgG and anti-S IgA were almost identical. Only the mean anti-S1/S2 IgG levels were higher after receiving three mRNA vaccines. Based on these data, we can conclude that administering a third dose of BNT162b2 after two doses of BBIBP-CorV is an effective strategy to significantly enhance both humoral and T cell-mediated immune response, and its effectiveness is comparable to that of three BNT162b2 vaccines. [ABSTRACT FROM AUTHOR]

Vaccination against the seasonal influenza virus is the best way to prevent infection. Nevertheless, vaccine efficacy remains far from optimal especially in high-risk populations such as the elderly. Recent technological advancements have facilitated rapid and precise identification of the B and T cell epitopes that are targets for protective responses. While these discoveries have undoubtedly brought the field closer to “universal” influenza virus vaccines, choosing the correct antigen is only one piece of the equation. Achieving efficacy and durability requires a detailed understanding of the diverse host factors and pathways that are required for attaining optimal responses. Sequencing technologies, systems biology, and immunological studies have recently advanced our understanding of the diverse aspects of the host response required for vaccine efficacy. In this paper, we review the critical role of the host response in determining efficacious responses and discuss the gaps in knowledge that will need to be addressed if the field is to be successful in developing new and more effective influenza virus vaccines. [ABSTRACT FROM AUTHOR]

Immune defense against infection with the hepatitis B virus (HBV) is complex and involves both host innate and adaptive immune systems. It is well accepted that the development of sufficient HBV-specific T cell and B cell responses are required for controlling an HBV infection. However, the contribution of innate immunity to removing HBV has been explored in recent years. Toll-like receptors (TLRs) are recognized as the first line of antiviral immunity because they initiate intracellular signaling pathways to induce antiviral mediators such as interferons (IFNs) and other cytokines. Recent studies show that the activation of TLR-mediated signaling pathways results in a suppression of HBV replication in vitro and in vivo. However, HBV has also evolved strategies to counter TLR responses including the suppression of TLR expression and the blockage of downstream signaling pathways. Antiviral treatment in chronic HBV-infected patients leads to an upregulation of TLR expression and the restoration of its innate antiviral functions. Thus, TLR activation may serve as an additional immunotherapeutic option for treating chronic HBV infection in combination with antiviral treatment. [ABSTRACT FROM AUTHOR]

Vaccination against the seasonal influenza virus is the best way to prevent infection. Nevertheless, vaccine efficacy remains far from optimal especially in high-risk populations such as the elderly. Recent technological advancements have facilitated rapid and precise identification of the B and T cell epitopes that are targets for protective responses. While these discoveries have undoubtedly brought the field closer to “universal” influenza virus vaccines, choosing the correct antigen is only one piece of the equation. Achieving efficacy and durability requires a detailed understanding of the diverse host factors and pathways that are required for attaining optimal responses. Sequencing technologies, systems biology, and immunological studies have recently advanced our understanding of the diverse aspects of the host response required for vaccine efficacy. In this paper, we review the critical role of the host response in determining efficacious responses and discuss the gaps in knowledge that will need to be addressed if the field is to be successful in developing new and more effective influenza virus vaccines.

Human rotavirus (HRV) infection is a major cause of viral gastroenteritis in young children worldwide. Current oral vaccines perform poorly in developing countries where efficacious vaccines are needed the most. Therefore, an alternative affordable strategy to enhance efficacy of the current RV vaccines is necessary. This study evaluated the effects of colonization of neonatal gnotobiotic (Gn) pigs with Escherichia coli Nissle (EcN) 1917 and Lacticaseibacillus rhamnosus GG (LGG) probiotics on immunogenicity and protective efficacy of oral attenuated (Att) HRV vaccine. EcN-colonized pigs had reduced virulent HRV (VirHRV) shedding and decreased diarrhea severity compared with the LGG-colonized group. They also had enhanced HRV-specific IgA antibody titers in serum and antibody secreting cell numbers in tissues pre/post VirHRV challenge, HRV-specific IgA antibody titers in intestinal contents, and B-cell subpopulations in tissues post VirHRV challenge. EcN colonization also enhanced T-cell immune response, promoted dendritic cells and NK cell function, reduced production of proinflammatory cytokines/Toll like receptor (TLR), and increased production of immunoregulatory cytokines/TLR expression in various tissues pre/post VirHRV challenge. Thus, EcN probiotic adjuvant with AttHRV vaccine enhances the immunogenicity and protective efficacy of AttHRV to a greater extent than LGG and it can be used as a safe and economical oral vaccine adjuvant. [ABSTRACT FROM AUTHOR]

Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, current preventative strategies of vaccination against influenza virus often provide incomplete protection due the continuous antigenic drift/shift of circulating strains of influenza virus. Prevention and control of influenza virus infection with vaccines is dependent on the host immune response induced by vaccination and the various vaccine platforms induce different components of the local and systemic immune response. This review focuses on the immune basis of current (inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV)) as well as novel vaccine platforms against influenza virus. Particular emphasis will be placed on how each platform induces cross-protection against heterologous influenza viruses, as well as how this immunity compares to and contrasts from the "gold standard" of immunity generated by natural influenza virus infection. [ABSTRACT FROM AUTHOR]

Immune response to vaccinations in celiac patients is of growing scientific interest. However, some aspects of the relationship between celiac disease (CD) and vaccines are still unclear. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: "adaptive immunity", "celiac disease", "humoral immune response", "immunization", and "vaccination". To date, there is no evidence showing any causative association between vaccines and CD development. Therefore, vaccinations may be administered according to the modalities and timing of the National Immunization Schedule for each country. The rotavirus vaccine is currently recommended for the general population, and according to some data, it appears to reduce the risk for the development of CD autoimmunity in the early years of life. Regarding the hepatitis B virus, a booster dose of the vaccine is often required due to the low or the lost immune response rate in CD. Furthermore, determination of hepatitis B antibody titers could be useful in newly diagnosed CD subjects regardless of age at diagnosis. Finally, pneumococcal vaccines may be administered in patients with advancing age at diagnosis and concomitant risk factors. Future clinical practice guidelines for vaccination and monitoring programs in celiac patients could be recommended. [ABSTRACT FROM AUTHOR]

The signaling lymphocytic activation molecule (SLAM) family of receptors are expressed on the majority of immune cells. These receptors often serve as self-ligands, and play important roles in cellular communication and adhesion, thus modulating immune responses. SLAM family receptor signaling is differentially regulated in various immune cell types, with responses generally being determined by the presence or absence of two SLAM family adaptor proteins—Ewing's sarcoma-associated transcript 2 (EAT-2) and SLAM-associated adaptor protein (SAP). In addition to serving as direct regulators of the immune system, certain SLAM family members have also been identified as direct targets for specific microbes and viruses. Here, we will discuss the known roles for these receptors in the setting of viral infection, with special emphasis placed on HIV infection. Because HIV causes such complex dysregulation of the immune system, studies of the roles for SLAM family receptors in this context are particularly exciting. [ABSTRACT FROM AUTHOR]