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The rapid development of vaccines is a crucial objective in modern biotechnology and molecular pharmacology. In this context, conducting research to expedite the selection of a potent immunogen is imperative. The candidate vaccine should induce the production of antibodies that can recognize the immunogenic epitopes of the target protein, resembling the ones found in recovered patients. One major challenge in vaccine development is the absence of straightforward and reliable techniques to determine the extent to which the spectrum of antibodies produced after vaccination corresponds to antibodies found after recovery. This paper describes a newly developed method to detect antibodies specific to immunogenic epitopes of the target protein in blood plasma and to compare them with antibody spectra generated post vaccination. Comparing the antibody pool generated in the human body after recovering from an infectious disease with the pool formed through vaccination can become a universal method for screening candidate vaccines. This method will enable the identification of candidate vaccines that can induce the production of antibodies similar to those generated in response to a natural infection. Implementing this approach will facilitate the rapid development of new vaccines, even when faced with a pandemic. [ABSTRACT FROM AUTHOR]

Currently, allergen-specific immunotherapy (AIT) for ragweed allergy is still based on natural allergen extracts. This study aimed to analyse the ability of four commercially available AIT vaccines (CLUSTOID, TYRO-SIT, POLLINEX Quattro Plus and Diater Depot) regarding their ability to induce IgG antibodies against ragweed pollen allergens in rabbits. Accordingly, the IgG reactivity of AIT-induced rabbit sera was tested for ten different ragweed pollen allergens (Amb a 1, 3, 4, 5, 6, 8, 9, 10, 11 and 12) by an ELISA. Furthermore, the ability of rabbit AIT-specific sera to block allergic patients' IgE binding to relevant ragweed allergens (Amb a 1, 4, 6, 8 and 11) and to inhibit allergen-induced basophil activation was evaluated by an IgE inhibition ELISA and a mediator release assay. Only two AIT vaccines (Diater Depot > CLUSTOID) induced relevant IgG antibody levels to the major ragweed allergen Amb a 1. The IgG responses induced by the AIT vaccines against the other ragweed allergens were low and highly heterogeneous. Interestingly, the kinetics of IgG responses were different among the AIT vaccines and even within one AIT vaccine (Diater Depot) for Amb a 1 (long-lasting) versus Amb a 8 and Amb a 11 (short-lived). This could be due to variations in allergen contents, the immunogenicity of the allergens, and different immunization protocols. The IgE inhibition experiments showed that rabbit AIT-specific sera containing high allergen-specific IgG levels were able to inhibit patients' IgE binding and prevent the mediator release with Diater Depot. The high levels of allergen-specific IgG levels were associated with their ability to prevent the recognition of allergens by patients' IgE and allergen-induced basophil activation, indicating that the measurement of allergen-induced IgG could be a useful surrogate marker for the immunological efficacy of vaccines. Accordingly, the results of our study may be helpful for the selection of personalized AIT vaccination strategies for ragweed-allergic patients. [ABSTRACT FROM AUTHOR]

This study follows 99 subjects vaccinated with Pfizer/BioNTech COVID-19 vaccines over two years, with particular focus on the last year of observation (between days 360 and 720). The response to the vaccination was assessed with Diasorin's SARS-CoV-2 TrimericSpike IgG. Screening for SARS-CoV-2 infection was performed with Abbott's SARS-CoV-2 Nucleocapsid IgG immunoassay. Data from questionnaires were also analyzed. Two years after the first vaccine dose administration, 100% of the subjects were positive for anti-spike SARS-CoV-2 IgG and the median antibody level was still high (3600 BAU/mL), dropping insignificantly over the last year. Simultaneously, a substantial increase in seropositivity in anti-nucleocapsid SARS-CoV-2 IgG was noted, reaching 33%. There was no statistically significant agreement between anti-N seropositivity and reported COVID-19. Higher anti-spike concentrations and lower COVID-19 incidence was seen in the older vaccinees. It was noted that only subjects boosted between days 360 and 720 showed an increase in anti-spike IgG concentrations. The higher antibody concentrations (median 7440 BAU/mL) on day 360 were noted in participants not infected over the following year. Vaccination, including booster administrations, and natural, even unrecognized, contact with SARS-CoV-2 entwined two years after the primary vaccination, leading to high anti-spike antibody concentrations. [ABSTRACT FROM AUTHOR]

Public antibody responses have been found against many infectious agents. Structural convergence of public antibodies is usually determined by immunoglobulin V genes. Recently, a human antibody public class against SARS-CoV-2 was reported, where the D gene (IGHD3-22) encodes a common YYDxxG motif in heavy-chain complementarity-determining region 3 (CDR H3), which determines specificity for the receptor-binding domain (RBD). In this review, we discuss the isolation, structural characterization, and genetic analyses of this class of antibodies, which have been isolated from various cohorts of COVID-19 convalescents and vaccinees. All eleven YYDxxG antibodies with available structures target the SARS-CoV-2 RBD in a similar binding mode, where the CDR H3 dominates the interaction with antigen. The antibodies target a conserved site on the RBD that does not overlap with the receptor-binding site, but their particular angle of approach results in direct steric hindrance to receptor binding, which enables both neutralization potency and breadth. We also review the properties of CDR H3-dominant antibodies that target other human viruses. Overall, unlike most public antibodies, which are identified by their V gene usage, this newly discovered public class of YYDxxG antibodies is dominated by a D-gene-encoded motif and uncovers further opportunities for germline-targeting vaccine design. [ABSTRACT FROM AUTHOR]

Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now become endemic and is currently one of the important respiratory virus infections regularly affecting mankind. The assessment of immunity against SARS-CoV-2 and its variants is important for guiding active and passive immunization and SARS-CoV-2-specific treatment strategies. Methods: We here devised a novel flow cytometry-based diagnostic platform for the assessment of immunity against cell-bound virus antigens. This platform is based on a collection of HEK-293T cell lines which, as exemplified in our study, stably express the receptor-binding domains (RBDs) of the SARS-CoV-2 S-proteins of eight major SARS-CoV-2 variants, ranging from Wuhan-Hu-1 to Omicron. Results: RBD-expressing cell lines stably display comparable levels of RBD on the surface of HEK-293T cells, as shown with anti-FLAG-tag antibodies directed against a N-terminally introduced 3x-FLAG sequence while the functionality of RBD was proven by ACE2 binding. We exemplify the usefulness and specificity of the cell-based test by direct binding of IgG and IgA antibodies of SARS-CoV-2-exposed and/or vaccinated individuals in which the assay shows a wide linear performance range both at very low and very high serum antibody concentrations. In another application, i.e., antibody adsorption studies, the test proved to be a powerful tool for measuring the ratios of individual variant-specific antibodies. Conclusion: We have established a toolbox for measuring SARS-CoV-2-specific immunity against cell-bound virus antigens, which may be considered as an important addition to the armamentarium of SARS-CoV-2-specific diagnostic tests, allowing flexible and quick adaptation to new variants of concern. [ABSTRACT FROM AUTHOR]

Despite the successes in wild-type polio eradication, poor vaccine coverage in the DRC has led to the occurrence of circulating vaccine-derived poliovirus outbreaks. This cross-sectional population-based survey provides an update to previous poliovirus-neutralizing antibody seroprevalence studies in the DRC and quantifies risk factors for under-immunization and parental knowledge that guide vaccine decision making. Among the 964 children between 6 and 35 months in our survey, 43.8% (95% CI: 40.6–47.0%), 41.1% (38.0–44.2%), and 38.0% (34.9–41.0%) had protective neutralizing titers to polio types 1, 2, and 3, respectively. We found that 60.7% of parents reported knowing about polio, yet 25.6% reported knowing how it spreads. Our data supported the conclusion that polio outreach efforts were successfully connecting with communities—79.4% of participants had someone come to their home with information about polio, and 88.5% had heard of a polio vaccination campaign. Additionally, the odds of seroreactivity to only serotype 2 were far greater in health zones that had a history of supplementary immunization activities (SIAs) compared to health zones that did not. While SIAs may be reaching under-vaccinated communities as a whole, these results are a continuation of the downward trend of seroprevalence rates in this region. [ABSTRACT FROM AUTHOR]

Group A streptococcus (GAS) is a global pathogen associated with significant morbidity and mortality for which there is currently no licensed vaccine. Vaccine development has been slow, mostly due to safety concerns regarding streptococcal antigens associated with autoimmunity and related complications. For a GAS vaccine to be safe, it must be ensured that the antigens used in the vaccine do not elicit an antibody response that can cross-react with host tissues. In this study, we evaluated the safety of our GAS vaccine candidate called VaxiStrep in New Zealand White rabbits. VaxiStrep is a recombinant fusion protein comprised of streptococcal pyrogenic exotoxin A (SpeA) and exotoxin B (SpeB), also known as erythrogenic toxins, adsorbed to an aluminum adjuvant. The vaccine elicited a robust immune response against the two toxins in the rabbits without any adverse events or toxicity. No signs of autoimmune pathology were detected in the rabbits' brains, hearts, and kidneys via immunohistochemistry, and serum antibodies did not cross-react with cardiac or neuronal tissue proteins associated with rheumatic heart disease or Sydenham chorea (SC). This study further confirms that VaxiStrep does not elicit autoantibodies and is safe to be tested in a first-in-human trial. [ABSTRACT FROM AUTHOR]

The S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze various substrates, including nucleic acids, proteins, oligopeptides, polysaccharides, and some other molecules. In this study, antibody fractions with affinity for RBD and S-protein (RBD-IgG and S-IgG) were isolated from the blood of COVID-19 patients vaccinated with Sputnik V. The fractions were analyzed for their potential to hydrolyze 18-mer oligopeptides corresponding to linear fragments of the SARS-CoV-2 S-protein. Here, we show that the IgG antibodies hydrolyze six out of nine oligopeptides efficiently, with the antibodies of COVID-19-exposed donors demonstrating the most significant activity. The IgGs of control donors not exposed to SARS-CoV-2 were found to be inactive in oligopeptide hydrolysis. The antibodies of convalescents and vaccinated patients were found to hydrolyze oligopeptides in a wide pH range, with the optimal pH range between 6.5 and 7.5. The hydrolysis of most oligopeptides by RBD-IgG antibodies is inhibited by thiol protease inhibitors, whereas S-IgG active centers generally combine several types of proteolytic activities. Ca2+ ions increase the catalytic activity of IgG preparations containing metalloprotease-like active centers. Thus, the proteolytic activity of natural antibodies against the SARS-CoV-2 protein is believed to be due to the similarity of catalytic antibodies' active centers to canonical proteases. This work raises the question of the possible physiological role of proteolytic natural RBD-IgG and S-IgG resulting from vaccination and exposure to COVID-19. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate possible influencing factors based on the distribution of the pertussis toxin (PT) and filamentous hemagglutinin (FHA) antibody levels in 0–14-year-old children in Jiangsu Province, China, and to analyze changes in IgG antibody levels after pertussis vaccination in children over time via a restricted cubic spline (RCS)-fitted binary logistic regression model. We collected surveillance data on pertussis through the National Notifiable Disease Reporting System (NNDRS). Serum samples were collected, and PT IgG/FHA IgG antibody levels were determined via an enzyme-linked immunosorbent assay (ELISA). A binary logistic regression model was fitted with an RCS. Peak incidence occurred in children aged 0–1 years from 2007 to 2022, and a second peak emerged in children aged 5 years and older from 2018 onwards which shifted towards older age groups. The geometric mean concentrations (GMC) of the anti-PT IgG antibody and anti-FHA IgG antibody in 1129 patients were 15.13 (13.49–16.76) IU/mL and 22.99 (21.17–24.81) IU/mL, respectively. The seropositivity rates of the anti-PT IgG and anti-FHA IgG antibodies in the group receiving a full vaccination course (four doses) were significantly higher than those of other groups (24.6% vs. 43.3%). The RCS fitting model showed a non-linear relationship between the duration after immunization and the odds ratio (OR) of having PT-IgG and FHA-IgG antibody concentrations ≥20 IU/mL in children with documented immunization histories (1–4 doses) (Poverall < 0. 001; Pnonlinear ≤ 0.001). The children with histories of immunization demonstrated antibody levels that decreased to very low levels around 17 months after the last dose of the vaccine. Therefore, it is recommended that pertussis-containing vaccines be administered as booster immunizations for older children. [ABSTRACT FROM AUTHOR]

Aim: The objective of this study was to explore the potential correlation between COVID-19 infection or vaccination and levels of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. Methods: Among 6050 healthcare workers at the Ege University Hospital, a cohort study with 162 participants divided into three arms with 54 participants each was conducted. The three groups were selected as follows: those diagnosed with COVID-19 and not vaccinated (group 1), those diagnosed with COVID-19 and subsequently vaccinated with CoronaVac (group 2), and those not diagnosed with COVID-19 but vaccinated with two doses of CoronaVac (group 3). Antibody levels measured at the sixth month of follow-up were defined as the primary outcome. Results: At the sixth month, all serum samples tested positive for anti-S. Anti-S levels were found to be significantly higher in group 2 than in the other groups (p < 0.001). There were no differences in antibody levels between groups 1 and 3 (p = 0.080). Average antibody levels were found to be lower in office workers and males. Anti-N antibodies were found to be positive in 85.1% of subjects at the sixth month. In group 2, anti-N antibodies were detected in all samples at the sixth month. Anti-N antibody levels were not significantly different between groups 1 and 2 (p = 0.165). Groups 1 and 2 had significantly higher antibody levels than group 3 (p < 0.001). Conclusions: Vaccination or infection provide protection for at least 6 months. Those who have previously been diagnosed with COVID-19 do not need to be vaccinated in the early period before their antibody levels decrease. [ABSTRACT FROM AUTHOR]

For epidemiological studies of infectious diseases, pathogen-specific antibody levels in an area give us essential and appropriate information. The antibodies against pathogens are usually detected in blood, the drawing of which inconveniences people. Collection of blood increases the risk of accidental infections through blood, and it is difficult to obtain the participation of the target populations, especially the younger generation. On the other hand, urine samples, which contain a high enough level of antibodies for ELISA, can be harmlessly and easily collected and therefore have been used for epidemiological studies for diseases. The antibody examination of urine has been used for the epidemiology of parasitic diseases with a high sensitivity and specificity of serum samples. In this paper, we reviewed antibody assays with urine for seven parasitic diseases that urine diagnostic methods have reported in the past, and these are important infections included in NTDs, caused, for example, by Leishmania donovani, Wuchereria bancrofti, Schistosoma japonicum, Paragonimus westermani, Echinococcus granulosus, Echinococcus multilocularis, Strongyloides stercoralis, and Opisthorchis viverrini. The easy and safe urine surveillance system might be an admirable tool for future epidemiological studies for infectious diseases. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the dynamics, duration, and production of total and neutralizing antibodies induced by the BNT162b2 vaccine and the possible effect of gender and prior SARS-CoV-2 infection on the generation of these antibodies. Total antibodies were quantified via chemiluminescent microparticle immunoassay (CMIA), and neutralizing antibodies were quantified using the cPass SARS-CoV-2 kit. Individuals with a history of COVID-19 produced twice as many antibodies than vaccinated individuals without prior SARS-CoV-2 infection, with an exponential increase observed in just six days. In those without a COVID-19 history, similar antibody production was reached 45 days after vaccination. Although total antibodies decline considerably in the first two months, the neutralizing antibodies and their inhibitory capacity (>96%) persist up to 6 months after the first dose. There was a tendency for higher total antibodies in women than men, but not at the inhibition capacity level. We suggest that the decline in total antibodies should not be considered as an indicator of loss of protective immunity because most antibodies decay two months after the second dose, but neutralizing antibodies remain constant for at least six months. Therefore, these latter antibodies could be better indicators for estimating the time-dependent vaccine efficacy. [ABSTRACT FROM AUTHOR]

Anti-platelet factor 4 (anti-PF4) antibodies were identified as pathogenic antibodies for vaccine-induced immune thrombocytopenia and thrombosis (VITT) in subjects receiving ChAdOx1 nCoV-19 vaccinations. We performed a prospective cohort study to determine the prevalence of anti-PF4 and the effect of the ChAdOx1 nCoV-19 vaccine on anti-PF4 in healthy Thai subjects. Anti-PF4 antibodies were measured before and four weeks after receiving the first vaccination. Participants with detectable antibodies were scheduled for repeat anti-PF4 analysis at 12 weeks after the second vaccination. Of 396 participants, ten participants (2.53%; 95% confidence interval [CI], 1.22–4.59) were positive for anti-PF4 before receiving vaccinations. Twelve people (3.03%; 95% CI, 1.58–5.23) had detectable anti-PF4 after the first vaccination. There was no difference in the optical density (OD) values of anti-PF4 antibodies when comparisons were made between pre-vaccination and four weeks after the first vaccination (p = 0.0779). There was also no significant difference in OD values in participants with detectable antibodies. No subjects experienced thrombotic complications. Pain at the injection site was associated with an increased risk of being anti-PF4 positive at an odds ratio of 3.44 (95% CI, 1.06–11.18). To conclude, the prevalence of anti-PF4 was low in Thais and did not significantly change over time. [ABSTRACT FROM AUTHOR]

RSV is divided into two antigenic subtypes, RSV A and RSV B, which is largely based on the variation in the G protein, while the fusion protein F is more conserved and a target for antibody-mediated neutralization. Here we evaluate the breadth of the protective immune responses across RSV A and RSV B subtypes, induced by vaccines based on the RSV A-based fusion protein, stabilized in the prefusion conformation (preF) in preclinical models. Immunization of naïve cotton rats with preF subunit or preF encoded by a replication incompetent Adenoviral 26, induced antibodies capable of neutralizing recent RSV A and RSV B clinical isolates, as well as protective efficacy against a challenge with RSV A and RSV B strains. Similarly, induction of cross-neutralizing antibodies was observed after immunization with Ad26-encoded preF, preF protein or a mix of both (Ad26/preF protein) in RSV pre-exposed mice and African Green Monkeys. Transfer of serum of human subjects immunized with Ad26/preF protein into cotton rats provide protection against challenges with both RSV A and RSV B, with complete protection against both strains observed in the lower respiratory tract. In contrast, almost no protection against RSV A and B infection was observed after the transfer of a human serum pool isolated pre-vaccination. These results collectively show that the RSV A-based monovalent Ad26/preF protein vaccine induced neutralizing antibodies, as well as protection against both RSV A and RSV B subtypes in animals, including by passive transfer of human antibodies alone, suggesting that clinical efficacy against both subtypes can be achieved. [ABSTRACT FROM AUTHOR]

Vaccination during pregnancy could protect women and their infants from invasive Group B Streptococcus (GBS) disease. To understand if neonatal dried blood spots (DBS) can be used to determine the amount of maternally derived antibody that protects infants against invasive GBS disease, a retrospective case-control study was conducted in England between 1 April 2014 and 30 April 2015. The DBS of cases with invasive GBS disease (n = 61) were matched with healthy controls (n = 125). The haematocrit, DBS storage temperature, freeze-thaw cycle, and paired serum/DBS studies were set up to optimise the antibody assessment. The samples were analysed using a multiplex immunoassay, and the results were assessed using parametric and nonparametric tests. Antibody concentrations were stable at haematocrits of up to 50% but declined at 75%. DBS storage at room temperature was stable for three months compared with storage from collection at −20 °C and rapidly degraded thereafter. Total IgG levels measured in DBS and paired serum showed a good correlation (r2 = 0.99). However, due to suboptimal storage conditions, no difference was found in the GBS IgG levels between DBS samples from cases and controls. We have demonstrated a proof of concept that assays utilising DBS for assessing GBS serotype-specific antibodies in infants is viable. This method could be used to facilitate future large sero-correlate studies, but DBS samples must be stored at −20 °C for long term preservation of antibody. [ABSTRACT FROM AUTHOR]

This study pictures the humoral response of 100 vaccinees to Pfizer/BioNTech COVID-19 vaccine over a year, with particular focus on the influence of a booster shot administered around 10 months after the primary immunization. The response to the vaccination was assessed with Diasorin's SARS-CoV-2 TrimericSpike IgG. Abbott's SARS-CoV-2 Nucleocapsid IgG immunoassay was used to identify SARS-CoV-2 contact, even asymptomatic. In contrast to the gradual decline of the anti-spike IgG between 30 and 240 days after the first dose, an increase was noted between days 240 and 360 in the whole cohort. However, a statistically significant rise was seen only in boosted individuals, and this effect of the booster decreased over time. An increase was also observed in non-boosted but recently infected participants and a decrease was reported in non-boosted, non-infected subjects. These changes were not statistically significant. On day 360, a percentage of new SARS-CoV-2 infections was statistically lower in the boosted vs. non-boosted subgroups. The booster immunization is the most efficient way of stimulating production of anti-spike, potentially neutralizing antibodies. The response is additionally enhanced by the natural contact with the virus. Individuals with a low level of anti-spike antibodies may benefit the most from the booster dose administration. [ABSTRACT FROM AUTHOR]

Measurement of strength and durability of SARS-COV-2 antibody response is important to understand the waning dynamics of immune response to both vaccines and infection. The study aimed to evaluate the level of IgG antibodies against SARS-CoV-2 and their persistence in recovered, naïve, and vaccinated individuals. We investigated anti-spike RBD IgG antibody responses in 10,000 individuals, both following infection with SARS-CoV-2 and immunization with SARS-COV-2 AstraZeneca, Sputnik V, Sinopharm, and Sinovac. The mean levels of anti-spike IgG antibodies were higher in vaccinated participants with prior COVID-19 than in individuals without prior COVID-19. Overall, antibody titers in recovered vaccinee and naïve vaccinee persisted beyond 20 weeks. Vaccination with adenoviral–vector vaccines (AstraZeneca and Sputnik V) generates higher antibody titers than with killed virus vaccine (Sinopharm and Sinovac). Approximately two-thirds of asymptomatic unvaccinated individuals had developed virus-specific antibodies. A single dose of vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with apparent prior SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals. In addition, the high number of seropositivity among asymptomatic unvaccinated individuals showed that the number of infections are probably highly underestimated. Those vaccinated with inactivated vaccine may require more frequent boosters than those vaccinated with adenoviral vaccine. These findings are important for formulating public health vaccination strategies during COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Host response to COVID-19 vaccines is partially evaluated through the estimation of antibody response, specifically the binding anti-spike (anti-S) and the neutralizing antibodies (nAbs) against SARS-CoV-2. Vaccine-induced humoral response affects decisions on the choice of vaccine type, vaccine acceptance, and the need for boosting. Identification of risk factors for poor antibody response helps to stratify individuals who might potentially require booster doses. The primary objective of this cross-sectional study was to investigate the antibody response after receiving two Sinopharm vaccine doses. Factors affecting antibody response were additionally studied. Moreover, a predictive cutoff for anti-S was generated to predict positivity of nAbs. Blood samples were collected from 92 adults and relevant data were recorded. Antibody levels (anti-S and nAbs) against SARS-CoV-2 were tested one month following the second dose of Sinopharm vaccine using two commercial ELISA tests. Among the 92 participants, 88 tested positive for anti-S (95.7%), with a median level of 52.15 RU/mL (equivalent to 166.88 BAU/mL). Fewer participants (67.4%) were positive for nAbs, with a median percentage of inhibition (%IH) of 50.62% (24.05–84.36). A significant positive correlation existed between the titers of both antibodies (correlation coefficient = 0.875, p < 0.001). When the anti-S titer was greater than 40 RU/mL (128 BAU/mL), nAbs were also positive with a sensitivity of 80.6% and a specificity of 90%. Positive nAbs results were associated with a higher anti-S titers (62.1 RU/mL) compared to negative nAbs (mean anti-S titer of 18.6 RU/mL). History of COVID-19 infection was significantly associated with higher titers of anti-S (p = 0.043) and higher IH% of nAbs (p = 0.048). Hypertensive participants were found to have significantly higher median titers of anti-S (101.18 RU/mL) compared with non-hypertensive ones (42.15 RU/mL), p = 0.034. Post-vaccination headache was significantly higher among those with higher anti-S than those with relatively lower titers (98.82 versus 43.69 RU/mL, p = 0.048). It can be concluded that the Sinopharm vaccine produced high levels of binding antibodies but with low neutralizing abilities. Also, levels of anti-S titer greater than 40 RU/mL could adequately predict positivity of nAbs without need for their testing. [ABSTRACT FROM AUTHOR]

In a few months, the SARS-CoV-2 virus caused a worldwide COVID-19 pandemic. In Poland, 6 million cases of the disease and 113,000 deaths from COVID-19 have been reported. Healthcare workers (HCWs) constitute one of the main COVID-19 risk groups. The Microblot-Array COVID-19 IgG assay was used to detect antibodies against three major SARS-CoV-2 antigens: nucleocapsid (NCP), RBD, and Spike 2 (S2). The aim of our study was to determine the seroprevalence and titer of anti-SARS-CoV-2 IgG antibodies—NCP, RBD, and S2—as markers of the humoral response in vaccinated and unvaccinated HCWs. The study included 203 persons who were divided into four groups: "COVID-19 Vaccinated", "COVID-19 Unvaccinated", "Non-COVID-19 Vaccinated", and "Non-COVID-19 Unvaccinated". The obtained results indicate that both seroprevalence and the antibody titer are the highest in the "COVID-19 Vaccinated" group. There is no so-called sterile vaccination, and after 6 months from the second dose of vaccine, most vaccinated people have a fairly high level of antibodies. We suggest that multiple vaccination and continuous testing are necessary. The Microblot-Array assay can distinguish between antibodies acquired after infection and/or vaccination. [ABSTRACT FROM AUTHOR]

Essential agricultural workers work under occupational conditions that may increase the risk of SARS-CoV-2 exposure and transmission. Data from an agricultural worker cohort in Guatemala, and anti-SARS-CoV-2 nucleocapsid IgG (anti-N IgG) testing were used to estimate past infections and analyze risk factors associated with seropositivity at enrollment and association with SARS-CoV-2 infection. The stability of neutralizing antibody (NAb) responses were assessed in a subset of participants. The adjusted relative risk (aRR) for seroprevalence at enrollment was estimated accounting for correlations within worksites. At enrollment, 616 (46.2%) of 1334 (93.2%) participants had anti-N IgG results indicating prior SARS-CoV-2 infection. A cough ≤ 10 days prior to enrollment (aRR = 1.28, 95% CI: 1.13–1.46) and working as a packer (aRR = 2.00, 95% CI: 1.67–2.38) or packing manager within the plants (aRR = 1.82, 95% CI: 1.36–2.43) were associated with increased risk of seropositivity. COVID-19 incidence density among seronegative workers was 2.3/100 Person-Years (P-Y), higher than seropositive workers (0.4/100 P-Y). Most workers with follow-up NAb testing (65/77, 84%) exhibited a 95% average decrease in NAb titers in <6 months. While participants seropositive at baseline were less likely to experience a symptomatic SARS-CoV-2 infection during follow-up, NAb titers rapidly waned, underscoring the need for multipronged COVID-19 prevention strategies in the workplace, including vaccination. [ABSTRACT FROM AUTHOR]

Several polymorphisms within Fc receptors (FCR) have been described, some of which correlate with allograft function. In the current study, we determined three Fcγ receptor and five Fcα receptor dimorphisms in 47 kidney transplant recipients who had been vaccinated against Streptococcus pneumoniae. We analyzed if FCR genotypes correlated with pneumococcal antibodies and their serotype-specific opsonophagocytic function, tested prior to and at months 1 and 12 post-vaccination. In parallel, we assessed antibodies against HLA and MICA and determined kidney function. We observed that IgG2 antibodies against pneumococci at months 1 and 12 after vaccination and IgA antibodies at month 1 differed significantly between the carriers of the three genotypes of FCGR3A rs396991 (V158F, p = 0.02; 0.04 and 0.009, respectively). Moreover, the genotype of FCGR3A correlated with serotype-specific opsonophagocytic function, reaching statistical significance (p < 0.05) at month 1 for 9/13 serotypes and at month 12 for 6/13 serotypes. Heterozygotes for FCGR3A had the lowest antibody response after pneumococcal vaccination. On the contrary, heterozygotes tended to have more antibodies against HLA class I and impaired kidney function. Taken together, our current data indicate that heterozygosity for FCGR3A may be unfavorable in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Multiple factors may be associated with immune responses to SARS-CoV-2 vaccines. Factors potentially related to magnitude and durability of response include age, time, and vaccine reactogenicity. This study analyzed SARS-CoV-2 IgG spike antibody responses following the second dose of vaccine in healthcare workers (HCWs). Data were collected from participants enrolled in a longitudinal SARS-CoV-2 serology study over a 12-month period. Participants completed a survey documenting symptoms post-vaccination. Serum specimens were tested for SARS-CoV-2 IgG antibodies using the Abbott Architect AdvisdeDx SARS-CoV-2 IgGII assay. Antibody levels were compared against time from second vaccine dose, and symptoms following vaccination. Altogether, 335 women (86.6%) and 52 men (13.4%) participated. Median age was 37 years (IQR 30-43). Overall median antibody level was 2150.80 [1246.12, 3556.98] AU/mL (IQR). Age was not associated with antibody concentration (p-value = 0.10). Higher antibody responses (2253 AU/mL vs. 1506 AU/mL; p = 0.008) were found in HCWs with one or more symptoms after the second dose of the vaccine (n = 311). Antibody responses persisted throughout the study period post-vaccination; statistically significant decreases in antibody responses were observed over time (p < 0.001). Higher antibody response was associated with reactogenicity post-vaccine. Age and sex were not associated with higher antibody responses. [ABSTRACT FROM AUTHOR]

Since 2019, the coronavirus disease 2019 (COVID-19) global pandemic has caused more than 300 million cases of disease and 5 million deaths. Vaccination has been widely accepted as the most effective measure for the prevention and control of this disease. However, there is little understanding about serum anti-SARS-CoV-2 IgM/IgG levels after inactivated vaccination as well as the relationship with peripheral blood leukocytes in the non-COVID-19 infected population. A total of 16,335 male and 22,302 female participants were recruited in this study, which was conducted in the Peking University Third Hospital located in Beijing (China). The level and seroprevalence of serum anti-SARS-CoV-2 receptor-binding domain (RBD) IgM/IgG and the association with peripheral blood leukocytes classification were investigated. With an increase in the number and percentage of full immunization of COVID-19 vaccinations in Beijing, serum anti-SARS-CoV-2 IgG antibodies levels and seroprevalence were significantly elevated (p < 0.01). The serum anti-SARS-CoV-2 IgG antibodies of 60 years and older persons were significantly lower than that of individuals that are 18~60 years old (p < 0.01), and there was a positive relationship between serum anti-SARS-CoV-2 IgG antibodies levels and peripheral blood lymphocyte count. The investigation of serum anti-SARS-CoV-2 IgM/IgG antibodies and the peripheral hematological index may prompt and help understand the adaptive immune response of vaccination. [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]

Unlike many other viruses, HIV-1 is highly variable. The structure of the viral envelope changes as the infection progresses and is one of the biggest obstacles in developing an HIV-1 vaccine. HIV-1 infection can cause the production of various natural autoantibodies, including catalytic antibodies hydrolyzing DNA, myelin basic protein, histones, HIV-integrase, HIV-reverse transcriptase, β-casein, serum albumin, and some other natural substrates. Currently, there are various directions for the development of HIV-1 vaccines: stimulation of the immune response on the mucous membranes; induction of cytotoxic T cells, which lyse infected cells and hold back HIV-infection; immunization with recombinant Env proteins or vectors encoding Env; mRNA-based vaccines and some others. However, despite many attempts to develop an HIV-1 vaccine, none have been successful. Here we review the entire spectrum of antibodies found in HIV-infected patients, including neutralizing antibodies specific to various viral epitopes, as well as antibodies formed against various autoantigens, catalytic antibodies against autoantigens, and some viral proteins. We consider various promising targets for developing a vaccine that will not produce unwanted antibodies in vaccinated patients. In addition, we review common problems in the development of a vaccine against HIV-1. [ABSTRACT FROM AUTHOR]

Correction: Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection. The group of mice vaccinated with only EDIII predominantly produced IgG1 while EDIII coupled to VLP (CuMVtt-EDIII) also induced IgG2a and IgG2b. Reference 1 Cabral-Miranda G., Lim S.M., Mohsen M.O., Pobelov I.V., Roesti E.S., Heath M.D., Skinner M.A., Kramer M.F., Martina B.E.E., Bachmann M.F. Zika Virus-Derived E-DIII Protein Displayed on Immunologically Optimized VLPs Induces Neutralizing Antibodies without Causing Enhancement of Dengue Virus Infection. [Extracted from the article]

Burkholderia mallei is a Gram-negative, non-motile, facultative intracellular bacillus and the causative agent of glanders, a highly contagious zoonotic disease. B. mallei is naturally resistant to multiple antibiotics and there is concern for its potential use as a bioweapon, making the development of a vaccine against B. mallei of critical importance. We have previously demonstrated that immunization with multivalent outer membrane vesicles (OMV) derived from B. pseudomallei provide significant protection against pneumonic melioidosis. Given that many virulence determinants are highly conserved between the two species, we sought to determine if the B. pseudomallei OMV vaccine could cross-protect against B. mallei. We immunized C57Bl/6 mice and rhesus macaques with B. pseudomallei OMVs and subsequently challenged animals with aerosolized B. mallei. Immunization with B. pseudomallei OMVs significantly protected mice against B. mallei and the protection observed was comparable to that achieved with a live attenuated vaccine. OMV immunization induced the production of B.mallei-specific serum IgG and a mixed Th1/Th17 CD4 and CD8 T cell response in mice. Additionally, immunization of rhesus macaques with B. pseudomallei OMVs provided protection against glanders and induced B.mallei-specific serum IgG in non-human primates. These results demonstrate the ability of the multivalent OMV vaccine platform to elicit cross-protection against closely-related intracellular pathogens and to induce robust humoral and cellular immune responses against shared protective antigens. [ABSTRACT FROM AUTHOR]

Adjuvants are key components in vaccines, they help in reducing the required antigen dose but also modulate the phenotype of the induced immune response. We previously showed that GPI-0100, a saponin-derived adjuvant, enhances antigen-specific mucosal and systemic antibody responses to influenza subunit and whole inactivated influenza virus (WIV) vaccine administered via the pulmonary route. However, the impact of the GPI-0100 dose on immune stimulation and the immune mechanisms stimulated by GPI-0100 along with antigen are poorly understood. Therefore, in this study we immunized C57BL/6 mice via the pulmonary route with vaccine consisting of WIV combined with increasing amounts of GPI-0100, formulated as a dry powder. Adjuvantation of WIV enhanced influenza-specific mucosal and systemic immune responses, with intermediate doses of 5 and 7.5 μg GPI-0100 being most effective. The predominant antibody subtype induced by GPI-0100-adjuvanted vaccine was IgG1. Compared to non-adjuvanted vaccine, GPI-0100-adjuvanted WIV vaccine gave rise to higher numbers of antigen-specific IgA- but not IgG-producing B cells in the lungs along with better mucosal and systemic memory B cell responses. The GPI-0100 dose was negatively correlated with the number of influenza-specific IFN- and IL17-producing T cells and positively correlated with the number of IL4-producing T cells observed after immunization and challenge. Overall, our results show that adjuvantation of pulmonary-delivered WIV with GPI-0100 mostly affects B cell responses and effectively induces B cell memory. [ABSTRACT FROM AUTHOR]

Healthcare workers (HCWs), as frontliners, are assumed to be among the highest risk groups for COVID-19 infection, especially HCWs directly involved in patient care. However, the data on the COVID-19 infection and seroprevalence rates are limited in HCWs. Therefore, we aimed to evaluate the seroprevalence rates in HCWs according to risk groups for COVID-19 contraction in a large cross-sectional study from a tertiary care hospital in Turkey. We enrolled 1974 HCWs before the vaccination programs. In two separate semi-quantitative ELISAs, either IgA or IgG antibodies against SARS-CoV-2 spike protein subunit 1 (S1) were measured. The proportion of positive test results for IgG, IgA, or both against SARS-CoV-2 of study subjects was 19% (375/1974). Frontline HCWs who had contact with patients (21.7%, RR 2.1 [1.51–2.92]) and HCWs in working in the COVID-19 units, intensive care units, or emergency department (19.7%, RR 1.61 [1.12–2.32]) had a notably higher Anti-SARS-CoV-2 IgG compared to the rest of HCWs who has no daily patient contacts ([11.1%]; p < 0.0001). HCWs who care for regular patients in the medium-risk group have also experienced a sustained higher risk of exposure to SARS-CoV-2. We should enhance the precaution against COVID-19 to protect HCW's safety through challenging times. [ABSTRACT FROM AUTHOR]

This study investigated the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies following inoculation with the coronavirus disease (COVID-19) vaccine. From June to July 2021, 127 participants who had completed COVID-19 vaccination (inactivated SARS-CoV-2 vaccine, 64; CoronaVac, 61; CanSino, 2) were recruited and tested using SARS-CoV-2 neutralizing antibody kits. The positive detection rate (inhibition of neutralizing antibodies ≥ 30%) was calculated and stratified according to population characteristics and inoculation time. The positive rate of neutralizing antibody was 47.22% (17/36) in men and 53.85% (49/91) in women, and 54.55% (24/44) in BMI ≥ 24 and 50.60% (42/83) in BMI < 24. Age was stratified as 20–29, 30–39, 40–49, and ≥50; positive detection rates of SARS-CoV-2 neutralizing antibodies were observed in 60.00% (24/40), 50.00% (21/42), 48.39% (15/31), and 42.86% (6/14), respectively, but with no significant difference (x2 = 1.724, p = 0.632). Among 127 vaccinated participants, 66 (51.97%) were positive. The positive detection rate was 63.93% (39/61) with CoronaVac and 42.19% (27/64) with the inactivated SARS-CoV-2 vaccine (significance x2 = 5.927, p = 0.015). Multivariate analysis revealed a significant difference in vaccination times, with average vaccination weeks in the positive and negative groups of 11.57 ± 6.48 and 17.87 ± 9.17, respectively (t= −4.501, p < 0.001). The positive neutralizing antibody rate was 100.00%, 60.00%, 58.33%, 55.56%, 43.14%, 28.57%, and 0.00% at 2–4, 5–8, 9–12, 13–16,17–20, 21–24, and >24 weeks, respectively (x2 = 18.030, p = 0.006). Neutralizing antibodies were detected after COVID-19 inoculation, with differences relating to inoculation timing. This study provides a reference for vaccine evaluation and follow-up immunization strengthening. [ABSTRACT FROM AUTHOR]

Data about the long-term duration of antibodies after SARS-CoV-2 vaccination are still scarce and are important to design vaccination strategies. In this study, 231 healthcare professionals received the two-dose regimen of BNT162b2. Of these, 158 were seronegative and 73 were seropositive at baseline. Samples were collected at several time points. The neutralizing antibodies (NAbs) and antibodies against the nucleocapsid and the spike protein of SARS-CoV-2 were measured. At day 180, a significant antibody decline was observed in seronegative (−55.4% with total antibody assay; −89.6% with IgG assay) and seropositive individuals (−74.8% with total antibody assay; −79.4% with IgG assay). The estimated half-life of IgG from the peak humoral response was 21 days (95% CI: 13–65) in seronegative and 53 days (95% CI: 40–79) in seropositive individuals. The estimated half-life of total antibodies was longer and ranged from 68 days (95% CI: 54–90) to 114 days (95% CI: 87–167) in seropositive and seronegative individuals, respectively. The decline of NAbs was more pronounced (−98.6%) and around 45% of the subjects tested were negative at day 180. Whether this decrease correlates with an equivalent drop in the clinical effectiveness against the virus would require appropriate clinical studies. [ABSTRACT FROM AUTHOR]

This is the first study outside of clinical trials (phase I–III) evaluating the ability of the Ad5-nCoV vaccine to generate neutralizing antibodies and the factors associated with optimal or suboptimal response. In a longitudinal assay, 346 people (117 with prior COVID-19 and 229 without prior COVID-19) vaccinated with Ad5-nCoV were recruited. The percentage of neutralizing antibodies against SARS-CoV-2 (Surrogate Virus Neutralization Test) and antibodies against Ad5 (ADV-Ad5 IgG ELISA) were quantified pre and post-vaccination effects. The Ad5-nCoV vaccine induces higher neutralizing antibodies percentage in individuals with prior COVID-19 than those without prior COVID-19 (median [IQR]: 98% [97–98.1] vs. 72% [54–90], respectively; p < 0.0001). Furthermore, a natural infection (before vaccination) induces more neutralizing antibodies percentage than immunized individuals without prior COVID-19 (p < 0.01). No patient had vaccine-severe adverse effects. The age, antidepressant, and immunosuppressive treatments, reactogenicity, and history of COVID-19 are associated with impaired antibody production. The anti-Ad5 antibodies increased after 21 days of post-vaccination in all groups (p < 0.01). We recommend the application of a booster dose of Ad5-nCoV, especially for those individuals without previous COVID-19 infection. Finally, the induction of anti-Ad5 antibodies after vaccination should be considered if a booster with the same vaccine is planned. [ABSTRACT FROM AUTHOR]

This case reports on the successful maternal to fetal transfer of neutralizing antibodies after vaccination with BNT162b2 in a pregnant woman at 25 weeks of gestation. The levels of neutralizing antibodies were approximately 5-fold higher in the umbilical cord than in the maternal blood while the level of total antibodies showed only a 2-fold increase. This suggest that the antibodies that crossed the syncytiotrophoblast cell barrier have specific characteristics that correlate to functional neutralizing capacity. Although pregnant and lactating women have been excluded from clinical trials for several reasons including ethical concerns about fetal exposure, accumulating evidence has now revealed that these vaccines are safe and efficient for both the fetus and the woman. Vaccination against COVID-19 in pregnancy is vital to control disease burden and to decrease morbidity in the ante-, peri- and post-natal periods. Inclusion of pregnant women in research programs for the development of SARS-CoV-2 vaccines should be mandatory to provide this population with the equitable benefits of vaccine research. [ABSTRACT FROM AUTHOR]

Vaccines are a crucial part of the global anti-pandemic effort against COVID-19. The effects of vaccines, as well as their common influencing factors, are the most important issues that we should focus on at this time. To this end, we review statistics on immunogenicity after vaccination, using neutralizing antibodies as the main reference index. Age, infection history, and virus variants are compared, and vaccination program recommendations are made accordingly. Suggestions are made to address concerns raised by the vaccines' shortened development cycle, as well as the emergence of immunity escape of viral variants. Finally, a brief description and future prospects are provided based on the principle of the ADE effect and previous experience with similar viruses. [ABSTRACT FROM AUTHOR]

Background: The introduction of the vaccination against SARS-CoV-2 infection creates the need for precise tools for the quality control of vaccination procedures, detection of poor humoral response, and estimation of the achieved protection against the disease. Thus, the study aimed to compare the results of the anti-SARS-CoV-2 tests to evaluate the application of the WHO standard unitage (the binding antibody units; BAU/mL) for a measurement of response to the vaccination. Methods: Patients undergoing vaccination against SARS-CoV-2 with Pfizer/BioNTech BNT162b2 (BNT162b2) (n = 79), referred for SARS-CoV-2 antibody measurement prior to vaccination and 21 days after dose 1, and 8, 14, and 30 days after dose 2 were included. The sera were tested with three assays: Elecsys SARS-CoV-2 S (Roche), LIAISON® SARS-CoV-2 TrimericS IgG (DiaSorin), and SARS-CoV-2 IgG II Quant (Abbott). Results: The three assays showed varying correlations at different time points in the study. The overall agreement for all samples was moderate to high (ρ = 0.663–0.902). We observed the most uniform agreement for the day of dose 2 (ρ = 0.775–0.825), while it was least consistent for day 8 (ρ = −0.131–0.693) and 14 (ρ = −0.247–0.603) after dose 2. The dynamics of changes of the SARS-CoV-2 antibody levels in patients without history of prior SARS-CoV-2 infection appears homogenous based on the Roche results, more heterogenous when considering the DiaSorin results, and in between for the Abbott results. Conclusions: The results highlight the need for further work on the international standard of measurement of SARS-CoV-2 Ig, especially in the era of vaccination. The serological assays can be useful to detect IgG/IgM antibodies to assess the response to the vaccination. However, they cannot be used interchangeably. In terms of the evaluation of the immune response to the BNT162b2 vaccine, Roche and Abbott kits appear to be more useful. [ABSTRACT FROM AUTHOR]

Objective: The objective of this research is to demonstrate the release of SARS-CoV-2 Spike (S) antibodies in human milk samples obtained by patients who have been vaccinated with mRNABNT162b2 vaccine. Methods: Milk and serum samples were collected in 10 volunteers 20 days after the first dose and 7 seven days after the second dose of the mRNABNT162b2 vaccine. Anti-SARS-CoV-2 S antibodies were measured by the Elecsys® Anti-SARS-CoV-2 S ECLIA assay (Roche Diagnostics AG, Rotkreuz, Switzerland), a quantitative electrochemiluminescence immunometric method. Results: At first sample, anti-SARS-CoV-2 S antibodies were detected in all serum samples (103.9 ± 54.9 U/mL) and only in two (40%) milk samples with a low concentration (1.2 ± 0.3 U/mL). At the second sample, collected 7 days after the second dose, anti-SARS-CoV-2 S antibodies were detected in all serum samples (3875.7 ± 3504.6 UI/mL) and in all milk samples (41.5 ± 47.5 UI/mL). No correlation was found between the level of serum and milk antibodies; the milk antibodies/serum antibodies ratio was on average 2% (range: 0.2–8.4%). Conclusion: We demonstrated a release of anti-SARS-CoV-2 S antibodies in the breast milk of women vaccinated with mRNABNT162b2. Vaccinating breastfeeding women could be a strategy to protect their infants from COVID-19 infection. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic caused by the novel coronavirus strain SARS-CoV-2 has already led to catastrophic consequences in global physical and psychological health, as well as economic recession [[1]] and its advance is ongoing [[2]]. If a vaccine is capable of triggering both neutralizing antibodies and T cells (CD8 T cells), it would likely provide stronger, long-lasting protection from SARS-CoV-2 virus infection. Cellular immune responses must be given appropriate attention in the analysis and reporting of COVID-19 vaccination trials, and research into vaccine platforms and adjuvants which may improve T-cell immunity is required to provide the best chance at widespread elimination of SARS-CoV-2. [Extracted from the article]

E2CD154 is a novel subunit vaccine candidate against classical swine fever virus (CSFV). It contains the E2 envelope protein from CSFV fused to the porcine CD154 molecule formulated in the oil adjuvant MontanideTM ISA50 V2. Previous works evidenced the safety and immunogenicity of this candidate. Here, two other important parameters related to vaccine efficacy were assessed. First, the existence of high maternally derived antibody (MDA) titers in piglets born to sows vaccinated with E2CD154 was demonstrated. These MDA titers remained above 1:200 during the first seven weeks of life. To assess whether the titers interfere with active vaccination, 79 piglets from sows immunized with either E2CD154 or a modified live vaccine were vaccinated with E2CD154 following a 0–21-day biphasic schedule. Animals immunized at either 15, 21, or 33 days of age responded to vaccination by eliciting protective neutralizing antibody (NAb) titers higher than 1:600, with a geometric mean of 1:4335, one week after the booster. Those protective levels of NAb were sustained up to six months of age. No vaccination-related adverse effects were described. As a conclusion, E2CD154 is able to induce protective NAb in piglets with different MDA levels and at different days of age. [ABSTRACT FROM AUTHOR]

Broadly neutralizing antibodies (bnAbs) isolated from HIV-infected individuals delineate vulnerable sites on the HIV envelope glycoprotein that are potential vaccine targets. A linear epitope within the N-terminal region of the HIV-1 fusion peptide (FP8) is the primary target of VRC34.01, a bnAb that neutralizes ~50% of primary HIV isolates. FP8 has attracted attention as a potential HIV vaccine target because it is a simple linear epitope. Here, platform technologies based on RNA bacteriophage virus-like particles (VLPs) were used to develop multivalent vaccines targeting the FP8 epitope. Both recombinant MS2 VLPs displaying the FP8 peptide and Qβ VLPs displaying chemically conjugated FP8 peptide induced high titers of FP8-specific antibodies in mice. Moreover, a heterologous prime-boost-boost regimen employing the two FP8-VLP vaccines and native envelope trimer was the most effective approach for eliciting HIV-1 neutralizing antibodies. Given the potent immunogenicity of VLP-based vaccines, this vaccination strategy—inspired by bnAb-guided epitope mapping, VLP bioengineering, and prime-boost immunization approaches—may be a useful strategy for eliciting bnAb responses against HIV. [ABSTRACT FROM AUTHOR]

The carbohydrate antigen dimeric Lewis X (DimLex), which accumulates in colonic and liver adenocarcinomas, is a valuable target to develop anti-cancer therapeutics. Using the native DimLex antigen as a vaccine would elicit an autoimmune response against the Lex antigen found on normal, healthy cells. Thus, we aim to study the immunogenic potential of DimLex and search internal epitopes displayed by DimLex that remain to be recognized by anti-DimLex monoclonal antibodies (mAbs) but no longer possess epitopes recognized by anti-Lex mAbs. In this context, we attempted to map the epitope recognized by anti-DimLex mAb SH2 by titrations and competitive inhibition experiments using oligosaccharide fragments of DimLex as well as Lex analogues. We compare our results with that reported for anti-Lex mAb SH1 and anti-polymeric Lex mAbs 1G5F6 and 291-2G3-A. While SH1 recognizes an epitope localized to the non-reducing end Lex trisaccharide, SH2, 1G5F6, and 291-2G3-A have greater affinity for DimLex conjugates than for Lex conjugates. We show, however, that the Lex trisaccharide is still an important recognition element for SH2, which (like 1G5F6 and 291-2G3-A) makes contacts with all three sugar units of Lex. In contrast to mAb SH1, anti-polymeric Lex mAbs make contact with the GlcNAc acetamido group, suggesting that epitopes extend further from the non-reducing end Lex. Results with SH2 show that this epitope is only recognized when DimLex is presented by glycoconjugates. We have reported that DimLex adopts two conformations around the β-d-GlcNAc-(1→3)-d-Gal bond connecting the Lex trisaccharides. We propose that only one of these conformations is recognized by SH2 and that this conformation is favored when the hexasaccharide is presented as part of a glycoconjugate such as DimLex-bovine serum albumin (DimLex-BSA). Proper presentation of the oligosaccharide candidate via conjugation to a protein or lipid is essential for the design of an anti-cancer vaccine or immunotherapeutic based on DimLex. [ABSTRACT FROM AUTHOR]

Gulf War illness (GWI) is a chronic disease of unknown etiology affecting over 200,000 veterans with symptoms including neurocognitive problems. We previously demonstrated GWI serum toxicity on neural cell cultures manifested by compromised neural network function, decreased cell spreading, and enhanced cell apoptosis. These patients lacked six human leukocyte antigen (HLA) class II alleles, resulting in an inability to form antibodies. Therefore, we hypothesized that GWI patients have vaccine-derived, persistent pathogens, which contribute to the development of the disease. Here, we examined whether individual vaccines were toxic in cultured N2A cells. Moreover, we used antibodies against each of the 20 vaccines administered to Gulf War (GW) veterans, to examine the effects of these antibodies on cell spreading and apoptosis in N2A cells. Antibodies against cholera toxin, hepatitis B, hemagglutinin H1N1, H3N2, and B from influenza A and B strains, measles, and Salmonella Typhi polysaccharide Vi had a remarkable protective effect on both cell spreading and apoptosis, whereas none of the other antibodies administered to GW veterans had an effect. The in vitro observed adverse effects of GWI serum may be due in part to vaccine-derived pathogens, antibodies against which had a protective effect in N2A cell cultures. [ABSTRACT FROM AUTHOR]

It has been 20 years since Newcastle disease virus (NDV) was first used as a vector. The past two decades have witnessed remarkable progress in vaccine generation based on the NDV vector and optimization of the vector. Protective antigens of a variety of pathogens have been expressed in the NDV vector to generate novel vaccines for animals and humans, highlighting a great potential of NDV as a vaccine vector. More importantly, the research work also unveils a major problem restraining the NDV vector vaccines in poultry, i.e., the interference from maternally derived antibody (MDA). Although many efforts have been taken to overcome MDA interference, a lack of understanding of the mechanism of vaccination inhibition by MDA in poultry still hinders vaccine improvement. In this review, we outline the history of NDV as a vaccine vector by highlighting some milestones. The recent advances in the development of NDV-vectored vaccines or therapeutics for animals and humans are discussed. Particularly, we focus on the mechanisms and hypotheses of vaccination inhibition by MDA and the efforts to circumvent MDA interference with the NDV vector vaccines. Perspectives to fill the gap of understanding concerning the mechanism of MDA interference in poultry and to improve the NDV vector vaccines are also proposed. [ABSTRACT FROM AUTHOR]

Influenza vaccine effectiveness varies annually due to the fast evolving seasonal influenza A(H3N2) strain and egg-derived mutations—both of which can cause a mismatch between the vaccine and circulating strains. To address these limitations, we have developed a hemagglutinin (HA)-based protein-detergent nanoparticle influenza vaccine (NIV) with a saponin-based Matrix-M™ adjuvant. In a phase 1 clinical trial of older adults, the vaccine demonstrated broadly cross-reactive A(H3N2) HA antibody responses. Two broadly neutralizing monoclonal antibodies derived from NIV-immunized mice were characterized by transmission electron microscopy (TEM), antibody competition assays, fluorescence-activated cell sorting (FACS) analysis, and protein–protein docking. These antibodies recognize two conserved regions of the head domain, namely the receptor binding site and the vestigial esterase subdomain, thus demonstrating the potential for an HA subunit vaccine to elicit antibodies targeting structurally and antigenically distinct but conserved sites. Antibody competition studies with sera from the phase 1 trial in older adults confirmed that humans also make antibodies to these two head domains and against the highly conserved stem domain. This data supports the potential of an adjuvanted recombinant HA nanoparticle vaccine to induce broadly protective immunity and improved vaccine efficacy. [ABSTRACT FROM AUTHOR]

Growing interest in universal influenza vaccines and novel administration routes has led to the development of alternative serological assays that are able to detect antibodies against conserved epitopes. We present a competitive ELISA method that is able to accurately determine the ratio of serum immunoglobulin G directed against the different domains of the hemagglutinin, the head and the stalk. Human serum samples were treated with two variants of the hemagglutinin protein from the A/California/7/2009 influenza virus. The signals detected were assigned to different groups of antibodies and presented as a ratio between head and stalk domains. A subset of selected sera was also tested by hemagglutination inhibition, single radial hemolysis, microneutralization, and enzyme-linked lectin assays. Pre-vaccination samples from adults showed a quite high presence of anti-stalk antibodies, and the results were substantially in line with those of the classical serological assays. By contrast, pre-vaccination samples from children did not present anti-stalk antibodies, and the majority of the anti-hemagglutinin antibodies that were detected after vaccination were directed against the head domain. The presented approach, when supported by further assays, can be used to assess the presence of specific anti-stalk antibodies and the potential boost of broadly protective antibodies, especially in the case of novel universal influenza vaccine approaches. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a flavivirus similar to Dengue virus (DENV) in terms of transmission and clinical manifestations, and usually both viruses are found to co-circulate. ZIKV is usually transmitted by mosquitoes bites, but may also be transmitted by blood transfusion, via the maternal–foetal route, and sexually. After 2015, when the most extensive outbreak of ZIKV had occurred in Brazil and subsequently spread throughout the rest of South America, it became evident that ZIKV infection during the first trimester of pregnancy was associated with microcephaly and other neurological complications in newborns. As a result, the development of a vaccine against ZIKV became an urgent goal. A major issue with DENV vaccines, and therefore likely also with ZIKV vaccines, is the induction of antibodies that fail to neutralize the virus properly and cause antibody-dependent enhancement (ADE) of the infection instead. It has previously been shown that antibodies against the third domain of the envelope protein (EDIII) induces optimally neutralizing antibodies with no evidence for ADE for other viral strains. Therefore, we generated a ZIKV vaccine based on the EDIII domain displayed on the immunologically optimized Cucumber mosaic virus (CuMVtt) derived virus-like particles (VLPs) formulated in dioleoyl phosphatidylserine (DOPS) as adjuvant. The vaccine induced high levels of specific IgG after a single injection. The antibodies were able to neutralise ZIKV without enhancing infection by DENV in vitro. Thus, the here described vaccine based on EDIII displayed on VLPs was able to stimulate production of antibodies specifically neutralizing ZIKV without potentially enhancing disease caused by DENV. [ABSTRACT FROM AUTHOR]

The construction of artificial proteins using conservative B-cell and T-cell epitopes is believed to be a promising approach for a vaccine design against diverse viral infections. This article describes the development of an artificial HIV-1 immunogen using a polyepitope immunogen design strategy. We developed a recombinant protein, referred to as nTBI, that contains epitopes recognized by broadly neutralizing HIV-1 antibodies (bNAbs) combined with Th-epitopes. This is a modified version of a previously designed artificial protein, TBI (T- and B-cell epitopes containing Immunogen), carrying four T- and five B-cell epitopes from HIV-1 Env and Gag proteins. To engineer the nTBI molecule, three B-cell epitopes of the TBI protein were replaced with the epitopes recognized by broadly neutralizing HIV-1 antibodies 10E8, 2F5, and a linear peptide mimic of VRC01 epitope. We showed that immunization of rabbits with the nTBI protein elicited antibodies that recognize HIV-1 proteins and were able to neutralize Env-pseudotyped SF162.LS HIV-1 strain (tier 1). Competition assay revealed that immunization of rabbits with nTBI induced mainly 10E8-like antibodies. Our findings support the use of nTBI protein as an immunogen with predefined favorable antigenic properties. [ABSTRACT FROM AUTHOR]

In transplant recipients vaccination against Streptococcus pneumoniae is recommended to reduce mortality from invasive pneumococcal disease. It is still debated if vaccination in transplant recipients triggers alloresponses. Therefore, it was our aim to define if vaccination with Prevenar 13®, a 13-valent, conjugated pneumococcal vaccine (Pfizer, New York, NY, USA) that acts T cell dependently, induces human leukocyte antigen (HLA) antibodies in clinically stable kidney transplant recipients. Forty-seven patients were vaccinated once with Prevenar 13® and HLA antibodies were determined prior to vaccination and at month 1 and 12 thereafter. In parallel, pneumococcal IgG antibodies were measured. Using Luminex™ Mixed Beads technology (One Lambda/Thermo Fisher, Canoga Park, CA, USA) we observed overall no change in HLA antibodies after vaccination. Pneumococcal antibodies increased significantly at month 1 (p < 0.0001) and remained elevated at month 12 (p < 0.005). A more detailed analysis of HLA antibodies showed that in 18 females HLA class I and II antibodies increased significantly at month 1 and 12 (p < 0.05); whereas in 29 males HLA class I and II antibodies tended to decrease. Using Luminex™ Single Antigen Beads assay, no de novo donor-specific HLA antibodies were detected after vaccination. In conclusion, the current data indicate that females may be more susceptible to the induction of (non-specific) HLA antibodies after vaccination. [ABSTRACT FROM AUTHOR]

Most human immunodeficiency virus (HIV) vaccine trials have lacked efficacy and empirical vaccine lead targets are scarce. Thus far, the only independent correlate of reduced risk of HIV-1 acquisition in humans is elevated levels of V2-specific antibodies identified in the modestly protective RV144 vaccine trial. Ten years after RV144, human and non-human primate vaccine studies have reassessed the potential contribution of V2-specific antibodies to vaccine efficacy. In addition, studies of natural HIV-1 infection in humans have provided insight into the development of V1V2-directed antibody responses and their impact on clinical parameters and disease progression. Functionally diverse anti-V2 monoclonal antibodies were isolated and their structurally distinct V2 epitope regions characterized. After RV144, a plethora of research studies were performed using different model systems, immunogens, protocols, and challenge viruses. These diverse studies failed to provide a clear picture regarding the contribution of V2 antibodies to vaccine efficacy. Here, we summarize the biological functions and clinical findings associated with V2-specific antibodies and discuss their impact on HIV vaccine research. [ABSTRACT FROM AUTHOR]

Hemagglutinin (HA) of influenza virus is a major target for vaccines. HA initiates the internalization of the virus into the host cell by binding to host sialic acid receptors; therefore, inhibition of HA can significantly prevent influenza virus infection. However, the high diversity of HA permits the influenza virus to escape from host immunity. Moreover, the vaccine efficacy is poor in some high-risk populations (e.g., elderly or immunocompromised patients). Passive immunization with anti-HA monoclonal antibodies (mAbs) is an attractive therapy; however, this method has high production costs and requires repeated inoculations. To address these issues, several methods for long-term expression of mAb against influenza virus have been developed. Here, we provide an overview of methods using plasmid and viral adeno-associated virus (AAV) vectors that have been modified for higher expression of neutralizing antibodies in the host. We also examine two methods of injection, electro-transfer and hydrodynamic injection. Our results show that antibody gene transfer is effective against influenza virus infection even in immunocompromised mice, and antibody expression was detected in the serum and upper respiratory tract. We also demonstrate this method to be effective following influenza virus infection. Finally, we discuss the perspective of passive immunization with antibody gene transfer for future clinical trials. [ABSTRACT FROM AUTHOR]