Vaccine-induced Antibodies Research Articles

Expert consensus on the benefits of neuraminidase in conventional influenza vaccines: a Delphi study

BackgroundSeasonal vaccination is the mainstay of human influenza prevention. Licensed influenza vaccines are regularly updated to account for viral mutations and antigenic drift and are standardised for their haemagglutinin content. However, vaccine effectiveness remains suboptimal. Neuraminidase (NA) evolves more gradually than hemagglutinin and has been demonstrated to provide added clinical benefits. However, NA is not currently a mandated or standardised component of influenza vaccines.MethodsHere, we collated expert opinions on the importance of NA in influenza vaccines in a two-stage Delphi survey. Nine statements about NA were formulated by a steering committee based on a targeted literature review. In the survey’s first round, panellists recruited from three continents were requested to report on their agreement with each statement and estimate the strength of evidence for each statement. Panellists were also requested to explain their choice of answer and suggest revisions to the statements. Consensus was considered reached if ≥ 75% of panellists agreed with a statement. If consensus was not reached for a statement, this statement was revised and included in the survey’s second round.ResultsNine panellists with a broad range of NA-related expertise, including clinical, research, and public health experience, completed the survey. They agreed that anti-NA responses acquired via natural infection or vaccination are associated with protective immunity independently of haemagglutinin and that NA provided additional advantages including improving disease severity metrics. The experts identified several knowledge gaps concerning heterologous cross-reactivity of vaccine-induced anti-NA antibodies, correlations between anti-NA titres and reduced transmission or infection risks, and differences in anti-NA responses to seasonal influenza vaccines.ConclusionsNA is an important influenza vaccine component and is associated with specific benefits. These benefits would likely be greater if NA content were standardised. Additional research is needed to optimise vaccines for anti-NA effects.

Variability in Vaccine Response and Trajectory in Early Childhood and Association with Demographic Variables, Antibiotic Exposure and Infection Proneness.

We sought to explore the variability of antibody responses to multiple vaccines during early life in individual children, assess the trajectory of each child longitudinally, determine the associations of demographic variables and antibiotic exposures with vaccine-induced immunity, and link vaccine responsiveness to infection proneness. In 357 prospectively-recruited children, age six through 36 months, antibody levels to 13 routine vaccine antigens were measured in sera at multiple time points and normalized to their respective protective thresholds to categorize children into four groups: very low, low, normal, and high vaccine responder. Demographic variables and frequency of antibiotic exposure data were collected. Participants were followed to determine change in vaccine groups over time and occurrences of infections. Vaccine-induced antibody levels persisted over time as very low, low, normal, or high in individual children and changed post-primary through post-booster immunizations against multiple antigen types, including toxoids, purified proteins, polysaccharide-protein conjugates, recombinant proteins and inactivated viruses. Factors influencing persistence or change in vaccine response group were assessed. Children who did not attend day care and African American/multiracial children had higher vaccine-induced antibody levels than White children. Children with lower vaccine-induced antibody levels had more frequent antibiotic exposures. Low vaccine responsiveness was linked to more frequent antibiotic-treated bacterial infections. When vaccine-induced antibody levels are used to define vaccine response groups, individual children may persist or change groups over time, which is associated with demographic variables and influenced by antibiotic exposures. Lower vaccine responsiveness can be linked to more frequent antibiotic-treated bacterial infections.

Sex differences in response to HBV vaccination in a cohort of health care workers.

Globally, healthcare workers (HCWs) are at greater risk of contracting Hepatitis B virus (HBV) infection than the general population, due to their frequent contact with blood or body fluids. For this reason, WHO underlined the importance of HBV immunization for all HCWs. Although sex is now considered one of the key factors influencing the intensity and duration of the immune response to vaccines, sex-specific analysis of vaccine-induced anti-HBs antibodies is rarely conducted. Our study aimed to evaluate the anti-HBs antibodies' long-lasting protective titers in male and female HCWs to identify sex differences in the humoral response to the HBV vaccine. The study was conducted on 2106 HCWs (1636 females and 470 males) working at the Padova University Hospital, Italy. Our results report significantly higher anti-HBs levels in female HCWs than in males, particularly when considering HCWs for whom the elapsed time since vaccination is greater than 10years, suggesting a greater persistence of anti-HBs in females. In conclusion, our findings could contribute to understanding differences in the antibody response to the HBV vaccine between male and female subjects and improving vaccination strategies for HCWs.

Booster Vaccination against Yellow Fever in Gambian children-(BoVY) -a Phase 3 clinical trial to establish safety and immunogenicity of repeated YF vaccination in healthy Gambian children of different ages

Background Yellow fever (YF) is a mosquito-borne and recently re-emerging viral haemorrhagic fever endemic to sub-Saharan Africa and South America. A highly effective vaccine against YF is licensed and recommended as part of routine childhood immunisation as a single dose at 9 months. Recent observational data demonstrate waning immunity following single primary vaccination and suggest that children in endemic areas may require booster vaccination. Methods This open-label, non-randomised clinical vaccine trial (ClinicalTrials.gov, NCT05332197, registered on 31 March 2022, URL: https://clinicaltrials.gov/study/NCT05332197) will assess the safety and immunogenicity of a booster dose of the licensed 17D YF vaccine in Gambian children. The trial will recruit 750 children in three cohorts of different ages (250 each). All children were vaccinated with the 17D YF vaccine at 9–10 months of age as part of clinical trials run by the Medical Research Council (MRC) Unit The Gambia, and are thus well-characterised, including basic clinical, anthropometric, and post-primary immunogenicity data. The children will receive booster doses at 15 months, 4 years, or 8.5 years. Serum samples will be taken before and 28 days after the booster, with additional sampling for exploratory endpoints in subgroups. Adverse events are solicited for the first three days following vaccination and recorded throughout the study period. The primary objective of the trial is to describe the safety and immunogenicity of the booster in the different age cohorts. Secondary objectives are to characterise the rate of sero-reversion (change from seropositive to seronegative) over a period of 9 months to 8 years following single primary vaccination and to profile the immune response to the booster to explore underlying mechanisms for the longevity of vaccine-induced antibody. Discussion The results of this trial are likely to directly impact WHO recommendations on whether booster vaccination is required for children in endemic areas, and if so, the optimal timing of such a booster.

A comparative study evaluating three line immunoassays available for serodiagnosis of equine Lyme borreliosis: Detection of Borrelia burgdorferi sensu lato-specific antibodies in serum samples of vaccinated and non-vaccinated horses

Diagnosis of equine Lyme borreliosis (LB), an infection caused by members of the Borrelia burgdorferi sensu lato complex (Bbsl), is challenging due to the nonspecific clinical signs of the disease and due to the variety of non-standardized serological tests. Specific vaccine-induced antibodies against LB, providing an effective protection against the infection, complicate the issue further. The standard for the detection of specific antibodies against Bbsl is a two-tier test system based on an enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent antibody test (IFA) for antibody screening combined with a qualitative, highly specific immunoassay (e. g. line immunoassay (LIA)) for confirmation. In this study, three LIAs available for detection of antibodies in equine serum samples were evaluated and compared. A total of 393 serum samples of 131 horses with known serostatus were used. It included groups of non-vaccinated horses, immunized horses (vaccinations against LB on days 0 and 14), and horses that had received an initial immunization plus an additional booster on day 180. Sera were collected on days 0, 135 and 210 of the study. Results were compared considering the tests’ sensitivity, specificity, diagnostic outcome, and the operability of each test. Agreements of the diagnostic results among the LIAs were calculated for overall test results and single antigen-antibody-complex signal results. They are presented as inter-rater agreement and statistic reliability, represented by the Fleiss’ kappa coefficient. Agreement scores ranged from poor to moderate depending on group and time-point of blood sample collection. Depending on LIA used, deficiencies were observed in the form of non-sufficient sensitivity of antigen signals on the LIA strips (especially for outer surface protein A (OspA) or variable major protein like sequence expressed (VlsE)) or as an inappropriate test interpretation of the OspA signal. Operability of the three LIAs was equally user-friendly with minor variations. In two LIAs, test-evaluation was simplified by a supplied scanner and evaluation software. To improve functionality of available LIAs for equine serum samples it is advisable to adjust sensitivity and specificity of single test antigen signals and establish appropriate evaluation protocols.

Comparative study of anti-SARS-CoV-2 receptor-binding domain total antibody titer before and after heterologous booster with mRNA-based COVID-19 vaccine

The waning immunity following the COVID-19 vaccination become a significant concern and the immunological dynamics of vaccine-induced antibodies after vaccination need to be explored. The aim of this study was to compare anti-SARS-CoV-2 receptor-binding domain (RBD) antibody levels before and after a booster dose with heterologous COVID-19 vaccine and to identify factors influencing the levels after receiving the booster dose. A cross-sectional study was conducted in which individuals who received primary doses of CoronaVac and a booster dose with an mRNA-based vaccine were recruited using a purposive sampling technique. The titers of anti-SARS-CoV-2 RBD antibodies were measured using an enzyme-linked immunosorbent assay (ELISA), and plausible associated factors were collected using a questionnaire-assisted face-to-face interview. The Wilcoxon test was used to compare the titers before and after the booster dose, while the Kruskal-Wallis and Mann-Whitney tests, followed by multivariate linear regression, were used to assess the factors associated with RBD total antibody titers. The results showed that there was a significant increase of anti-SARS-CoV-2 RBD total antibody titers before and after receiving the booster dose (1,558.7 BAU/mL vs 140.6 BAU/mL, p<0.001). The analysis revealed that age (p=0.555), sex (p=0.254), type of vaccine (p=0.914), presence of hypertension (p=0.541), diabetes (p=0.975), chronic obstructive pulmonary disease (COPD, p=0.620), and gout (p=0.364) were not associated with anti-SARS-CoV-2 RBD total antibody titers. However, the titers of anti-SARS-CoV-2 RBD total antibody were significantly different between those with and without hyperlipidemia (p=0.021). This study suggests that a booster dose with a heterologous COVID-19 vaccine could significantly enhance immune responses against COVID-19, and therefore, this strategy may be recommended as part of preventive measures to strengthen immunity against COVID-19.

Persistence of hepatitis E vaccine-induced antibody response across different dosage schedules and baseline serostatus

Hepatitis E virus (HEV) infection is a major cause of acute viral hepatitis worldwide. The efficacy and safety of the HEV239 vaccine have been validated, with protection lasting at least 10 years. This study extended the phase 3 trial of HEV239 (NCT01014845), presenting data on the durability of the anti-HEV IgG response elicited by one or two doses in the participants with different baseline serostatus. Over half of baseline seronegative individuals retained detectable antibodies at month 91 after two doses, with geometric mean concentration levels above the detection limit at month 67 (no available data for month 91). Seropositive individuals exhibited more prolonged and higher anti-HEV IgG response. After a single dose, individuals with pre-existing immunity achieved high and sustained antibody levels for over 103 months, comparable to the two-dose regimen. Both single-dose and two-dose HEV239 regimens demonstrated notable immunogenicity and persistence, potentially offering substantial protective benefits.

Longitudinal determination of seroprevalence and immune response to SARS-CoV-2 in a population of food and retail workers through decentralized testing and transformation of ELISA datasets.

Since the onset of the global COVID-19 pandemic in early 2020, numerous studies have been conducted worldwide to understand our immune response to the virus and to vaccination. This study investigates the humoral response elicited by SARS-CoV-2 infection and by vaccination in the poorly studied population of food and retail workers. These occupations were classified as essential by the Public Health Agency of Canada, potentially placing this population at greater risk of infection. Such a risk requires access to reliable and adaptable serological assays that can be rapidly deployed to guide public health strategies. Here we investigate the benefits and limitations of applying adaptable, decentralized tests for population-level immune surveillance in response to a pandemic, even before centralized testing is available. The 1.5-year study period spans from early 2021, when vaccination became available in this region, to mid-2022, following the emergence of the first Omicron variants. The cohort of 304 food and retail workers was recruited in the Québec City area. Participants attended five evenly spaced visits, providing blood samples as well as information on SARS-CoV-2 symptoms or risk factors, prior antigen or PCR test results and vaccination status, as well as work-related risk factors and protective measures. Parallel COVID-19 serological assays were performed using both a standardized chemiluminescent ELISA assay at the centralized platform operated in partnership with the Public Health Agency of Canada, and a semi-automated in-house colorimetric ELISA assay developed at our decentralized site. The YES/NO determination of SARS-CoV-2 vaccine seroconversion and/or infection events using the SARS-CoV-2 ancestral spike protein and nucleocapsid protein validated coherence of the centralized and decentralized assays. The flexibility of the decentralized assays allowed broadening the study to determine cross-reactivity of IgG directed against the spike protein of the SARS-CoV-2 Delta and Omicron VOCs, and IgM directed against the ancestral spike and nucleocapsid proteins. The nature of the data obtained in the decentralized assays allowed treatment with a recently developed mathematical transformation to obtain normal distribution, enabling ANOVA-Welsh statistical analysis. Although no significant differences were observed in humoral response as related to BMI, age, level of education, or chronic illnesses in this cohort of workers, statistically higher levels of vaccine-induced antibodies were observed for restaurant workers and hardware store workers in the early stages of the study, compared to workers in bars and grocery stores and in non-smokers versus smokers. This work highlights the importance of developing adaptable, decentralized tests for population-level immune surveillance in response to a pandemic, even before centralized testing is available. To our knowledge, no other study has reported such an extensive longitudinal investigation during key periods of the COVID-19 pandemic in a cohort of food and retail workers to analyze two types of immunoglobulin, three epitopes and antigens to three VOC. This study will inform strategies and measures to be implemented in the event of a future pandemic.

The Impact of HIV on B Cell Compartment and Its Implications for COVID-19 Vaccinations in People with HIV.

HIV causes intense polyclonal activation of B cells, resulting in increased numbers of spontaneously antibody-secreting cells in the circulation and hypergammaglobulinemia. It is accompanied by significant perturbations in various B cell subsets, such as increased frequencies of immature/transitional B cells, activated memory B cells, atypical memory B cells, short-lived plasmablasts and regulatory B cells, as well as by decreased frequencies of resting memory and resting naïve B cells. Furthermore, both memory and antigen-inexperienced naïve B cells show exhausted and immune-senescent phenotypes. HIV also drives the expansion and functional impairment of CD4+ T follicular helper cells, which provide help to B cells, crucial for the generation of germinal center reactions and production of long-lived plasma and memory B cells. By suppressing viral replication, anti-retroviral therapy reverses the virus-induced perturbations and functional defects, albeit inadequately. Due to HIV's lingering impact on B cells, immune senescence and residual chronic inflammation, people with HIV (PWH), especially immune non-responders, are immunocompromised and mount suboptimal antibody responses to vaccination for SARS-CoV-2. Here, we review how functionally and phenotypically distinct B cell subsets are induced in response to a vaccine and an infection and how HIV infection and anti-retroviral therapy (ART) impact them. We also review the role played by HIV-induced defects and perturbations in B cells in the induction of humoral immune responses to currently used anti-SARS-CoV-2 vaccines in PWH on ART. We also outline different strategies that could potentially enhance the vaccine-induced antibody responses in PWH. The review will provide guidance and impetus for further research to improve the immunogenicity of these vaccines in this human population.

MERS-CoV Spike Vaccine-induced N-Terminal Domain-specific Antibodies are More Protective than Receptor Binding Domain-specific Antibodies

MERS-CoV Spike Vaccine-induced N-Terminal Domain-specific Antibodies are More Protective than Receptor Binding Domain-specific Antibodies

Impact of Fasciola hepatica Infection and Triclabendazole Treatment on Humoral Immune Response in Cattle.

Fasciola hepatica is a trematode parasite of significant veterinary and public health importance, causing economic losses in livestock due to liver damage, weight loss and reduced milk production. Although triclabendazole (TCZ) is available for treatment, it does not prevent the disease or reinfection. Infected animals exhibit strong immunoregulation, increasing susceptibility to secondary infections and altering vaccine-induced antibody responses. This study investigates the humoral immune response in cattle infected with F. hepatica at different stages of infection and evaluates the effect of TCZ treatment on this response. It also examines how fasciolosis affects the antibody response induced by bacterial vaccines during early and chronic infection stages. Experimental infections in steers were conducted, with faecal and plasma samples collected at various intervals. The results showed a decrease in parasite-specific antibody avidity during infection. However, F. hepatica infection did not substantially modify antibody response to bacterial vaccines. This study underscores the need for further research on the impact of fasciolosis and its treatment on livestock vaccination efficacy.

A deep learning approach predicting the activity of COVID-19 therapeutics and vaccines against emerging variants

Understanding which viral variants evade neutralization is crucial for improving antibody-based treatments, especially with rapidly evolving viruses like SARS-CoV-2. Yet, conventional assays are labor intensive and cannot capture the full spectrum of variants. We present a deep learning approach to predict changes in neutralizing antibody activity of COVID-19 therapeutics and vaccine-elicited sera/plasma against emerging viral variants. Our approach leverages data of 67,885 unique SARS-CoV-2 Spike sequences and 7,069 in vitro assays. The resulting model accurately predicted fold changes in neutralizing activity (R2 = 0.77) for a test set (N = 980) of data collected up to eight months after the training data. Next, the model was used to predict changes in activity of current therapeutic and vaccine-induced antibodies against emerging SARS-CoV-2 lineages. Consistent with other work, we found significantly reduced activity against newer XBB descendants, notably EG.5, FL.1.5.1, and XBB.1.16; primarily attributed to the F456L spike mutation.

Association between long-term exposure to air pollutants with breakthrough SARS-CoV-2 infections and antibody responses among COVID-19 vaccinated older adults in Northern Italy

AimsTo investigate the association between long-term exposure to PM2.5, PM10, NO2 and O3 with SARS-CoV-2 breakthrough infections and COVID-19 vaccine-induced antibody responses in a northern Italian population-based sample of older adults. MethodsWithin an ongoing prospective population-based study, we followed-up 1326 vaccinated individuals aged 65–83 years, with no prior SARS-CoV-2 infection, for their first positive SARS-CoV-2 swab until December 31st, 2022. We assessed spike IgG antibody levels in most participants (n = 1206). The 2019 annual mean levels of air pollutants derived from combined use of chemical-transport and random-Forest models (spatial resolution: 1Kmq) were individually assigned based on the latest residence address. We estimated multivariable-adjusted associations (per 1 interquartile range increase, IQR) of air pollutants with breakthrough infections using Cox models with time-dependent vaccine exposure; and with percent change in the IgG geometric mean using generalized additive models. ResultsThe mean (SD) age was 74.9 ± 4.1 years, and 50% were women. An IQR (1.2 μg/m3) increase in long-term PM2.5 exposure was associated with a 52% increase in breakthrough infection risk following a second vaccine and a 26% increase following a third vaccine. The effect vanished with the further increment of vaccination doses. Associations for NO2 were inconsistent. Ozone was negatively associated with breakthrough infection risk, but this association reversed in bi-pollutant models adjusting for PM2.5. PM2.5 was associated with a −7.3% (−13.9% to −0.2%) reduction in vaccine-induced IgG levels. The reduction became more pronounced as the time delay from vaccination increased, and with adjustment for NO2 co-exposure. ConclusionIn our population of vaccinated older adults, fine particulate matter exposure was independently associated with a higher risk of SARS-CoV-2 breakthrough infection and a lower antibody response, both effects being influenced by timely and repeated vaccination schedule.

Exploring the sequence diversity and surface expression of Factor H-Binding Protein among invasive serogroup B meningococcal strains from selected European countries

ABSTRACT Factor H-Binding Protein (fHbp) is a key component of meningococcal vaccines such as MenB-fHbp, licensed in the EU, UK, and other countries. Sufficient expression of fHbp on the bacterial surface is necessary for vaccine-induced antibodies to bind and exert bactericidal activity. The flow cytometric MEASURE assay quantifies fHbp expression in vitro, and previous studies have shown that strains with a Mean Fluorescence Intensity (MFI) >1000 are likely to be killed by MenB-fHbp-induced antibodies. This study assessed fHbp peptide distribution and expression among 451 invasive group B strains collected in 2016 across England, Wales, and Northern Ireland (EW&NI), Germany, Italy, and Spain. We found that 92% of the strains expressed fHbp above the MFI 1000 threshold. The strain distribution across EW&NI, Germany, and Italy was similar, with coverage ranging from 92.1% to 94.6%, dominated by a small number of clonal complexes and fHbp peptides. Although, the Spanish subset had a higher proportion of lower-expressing strains, particularly clonal complex 213, resulting in a lower predicted coverage for Spain (84%). These results, along with other published MEASURE data, can provide a basis for genotypic MenB-fHbp coverage predictions, however, inclusion of the upstream intergenic sequence of the fHbp gene in the prediction improved its accuracy by distinguishing between low- and high-expressing strains. Future MEASURE analyses of strains with less common fHbp variants would serve to further refine vaccine coverage predictions.

A Novel Cell- and Virus-Free SARS-CoV-2 Neutralizing Antibody ELISA Based on Site-Specific Labeling Technology.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the global spread of coronavirus disease 2019 (COVID-19), creating an urgent need for updated methods to evaluate immune responses to vaccines and therapeutic strategies. In this study, we introduce a novel cell-free, virus-free SARS-CoV-2 neutralizing antibody ELISA (NAb-ELISA), which is based on competitive inhibition of the receptor binding domain (RBD) of spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor. In this method, site-specific biotinylated hACE2-Fc-Avi recombinant protein is immobilized onto a 96-well plate for capture, and the RBD-Fc-vHRP recombinant proteins serve as detection probes. Evaluation of sera from wild type (WT) or Delta RBD-immunized mice using the NAb-ELISA and pseudovirus neutralization tests (pVNTs) demonstrated strong correlations between assays (R2 = 0.91 and 0.90 for the WT and Delta groups, respectively). Additionally, the NAb-ELISA successfully detected cross-neutralizing activity in sera, though with slightly lower correlation to pVNT (R2 = 0.70-0.83). By employing NAb-ELISA instead of an indirect ELISA for hybridoma screening, five monoclonal antibodies (mAbs) with neutralizing activities against WT, Delta, and BA.2 pseudoviruses were obtained. This assay offers a straightforward, rapid, and safe approach to characterizing vaccine-induced antibody responses and mAb neutralization activity. Notably, the NAb-ELISA platform can be quickly adapted to assess neutralizing antibody responses against emerging mutant strains, addressing the rapid mutation of the virus.

Exposure to Pollutants and Vaccines' Effectiveness: A Systematic Review.

Background: Many human activities release harmful substances, contaminating the air, water, and soil. Since exposure to environmental pollutants is currently unavoidable, it is important to verify how these compounds may influence individual immune responses to vaccines. Methods: This review was conducted in accordance with the PRISMA statement. The protocol was registered on the PROSPERO platform with the following ID: CRD42024582592. We evaluated all observational, semi-experimental, and experimental studies written in both Italian and English that reported possible effects of exposure to environmental pollutants on the production of vaccine-induced antibodies. Results: Forty-two studies were included. The effects of pollutants were examined mainly in terms of antibody production in relation to mumps, measles and rubella, diphtheria and tetanus, hepatitis A and B, Haemophilus influenzae type B, influenza, tuberculosis, pertussis, Japanese encephalitis, poliomyelitis, and COVID-19 vaccines. Perfluorinated compounds were the most studied pollutants. Conclusions: Correlations between exposure to pollutants and reductions in antibody production were found in quite all the selected studies, suggesting that pollution control policies could contribute to increase the efficacy of vaccination campaigns. However, the heterogeneity of the examined studies did not allow us to perform a meta-analysis, and the literature on each type of vaccine or pollutant is still too limited to generate robust evidence. In order to confirm the findings of the present systematic review, and in the perspective of establishing possible exposure limit values for each type of pollutant, further research in this field is required.

STAR LIGHT Study: XBB.1.5 COVID-19 mRNA Vaccines Boost Systemic but Not Mucosal Immunity Against the SARS-CoV-2 JN.1 Variant in Patients with Chronic Liver Disease.

Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied. We present the first evaluation of XBB.1.5 COVID-19 vaccine immunogenicity against the SARS-CoV-2 JN.1 variant in patients with CLD. Serum anti-receptor binding domain (RBD) IgG, neutralization, and saliva anti-RBD IgG and IgA against wild-type SARS-CoV-2 (WT) and the XBB.1.5, EG.5.1, BA.2.86, and JN.1 variants were quantified before and 2-4 weeks following a fourth dose of XBB.1.5 mRNA vaccines. Vaccination boosted anti-RBD IgG and neutralization against all tested variants including JN.1 (each p < 0.001). Following immunization, neutralization was lower against JN.1 compared to WT, XBB.1.5, and EG.5.1 (p < 0.001, p < 0.001, and p < 0.01, respectively). Vaccination reduced neutralization failure rates against BA.2.86 and JN.1 (each p < 0.05). The evasion of vaccine-induced antibodies by the tested variants was low, indicated by the positive correlation between anti-RBD IgG and neutralization. At mucosal sites, vaccination boosted anti-RBD IgG (each p < 0.01) but failed to induce infection-blocking IgA (each p > 0.05). XBB.1.5 vaccines protect CLD patients against recent SARS-CoV-2 variants, but developing vaccines with optimized mucosal immunogenicity is required to prevent SARS-CoV-2 transmission and recurrent seasonal COVID-19 outbreaks.

Vaccine-induced human monoclonal antibodies to PfRH5 show broadly neutralizing activity against P. falciparum clinical isolates

Vaccines to the Plasmodium falciparum reticulocyte binding-like protein homologue 5 (PfRH5) target the blood-stage of the parasite life cycle. PfRH5 has the potential to trigger the production of strain-transcendent antibodies and has proven its efficacy both in pre-clinical and early clinical studies. Vaccine-induced monoclonal antibodies (mAbs) to PfRH5 showed promising outcomes against cultured P. falciparum laboratory strains from distinct geographic areas. Here, we assessed the functional impact of vaccine-induced anti-PfRH5 mAbs on more genetically diverse P. falciparum clinical isolates. We used mAbs previously isolated from single B cells of UK adult PfRH5 vaccinees and used ex-vivo growth inhibition activity (GIA) assays to assess their efficacy against P. falciparum clinical isolates. Next-generation sequencing (NGS) was used to assess the breadth of genetic diversity in P. falciparum clinical isolates and to infer the genotype/phenotype relationship involved in antibody susceptibility. We showed a dose-dependent inhibition of clinical isolates with three main GIA groups: high, medium and low. Except for one isolate, our data show no significant differences in the mAb GIA profile between P. falciparum clinical isolates and the 3D7 reference strain, which harbors the vaccine allele. We also observed an additive relationship for mAb combinations, whereby the combination of GIA-low and GIA-medium antibodies resulted in increased GIA, having important implications for the contribution of specific clones within polyclonal IgG responses. While our NGS analysis showed the occurrence of novel mutations in the pfrh5 gene, these mutations were predicted to have little or no functional impact on the antigen structure or recognition by known mAbs. Our present findings complement earlier reports on the strain transcendent potential of anti-PfRH5 mAbs and constitute, to our knowledge, the first report on the susceptibility of P. falciparum clinical isolates from natural infections to vaccine-induced human mAbs to PfRH5.

COVID-19 Vaccine-induced antibody response to BNT162b2 mRNA in frontline healthcare workers

The emergence of SARS-CoV-2, the virus causing COVID-19, has resulted in a pandemic that has disrupted all sectors of society. Less than a year after the sequencing of the virus’s genome, emergency use authorization for the BNT162b2 vaccine was requested. The aim of this study was to evaluate the response to the BNT162b2-mRNA COVID-19 vaccine in frontline workers from two hospitals in Colombia. Nasopharyngeal swabs were collected for the molecular detection of SARS-CoV-2 using real-time PCR, and blood samples were taken to assess seroconversion using qualitative and quantitative IgA, IgG, and IgM test kits. The study was conducted at a high-complexity healthcare institution in Bucaramanga, Colombia. 245 people were included in the first round and 129 in the second. SARS-CoV-2 molecular tests were conducted by RT-qPCR, and peripheral blood samples were collected to measure IgG, IgM, and IgA. The main outcome was to establish natural infection and the antibody response induced by the vaccine. The entire population was tested at two fixed times with RT-PCR tests and antibody level measurements approximately 4 and 8 months after receiving the second vaccine dose. 62 (25.3%) and 35 (14.3%) participants had a history of positive PCR in the first and second rounds, respectively. All positive cases showed elevated levels of all immunoglobulins, especially IgG. The average concentrations of IgA, IgM, and IgG at 90 days were 1149.5 U/mL (95% CI 828.2-1470.9); 320.3 U/mL (95% CI 218.4-422.3); and 9277.3 U/mL (95% CI 8989.2-9565.3). Frontline healthcare workers showed an adequate response to the BNT162b2 mRNA vaccine.

A novel orf virus vector-based COVID-19 booster vaccine shows cross-neutralizing activity in the absence of anti-vector neutralizing immunity

ABSTRACT Next-generation COVID-19 vaccines are being developed to expand the breadth of coverage against existing and future variants and to extend the duration of protection. Prime-2-CoV_Beta is an orf virus (ORFV) based multi-antigen COVID-19 vaccine that co-expresses Spike (S) and Nucleocapsid (N) antigens. The safety and immunogenicity of Prime-2-CoV_Beta is investigated in a phase 1 first-in-human (FIH) dose-finding trial (ORFEUS study, ClinicalTrials.gov: NCT05367843). Participants of two age groups (18–55 and 65–85 years) who previously completed at least two doses of mRNA vaccines were enrolled and sequentially assigned to different dose groups to receive one intramuscular dose of 3 × 105, 3 × 106, 1.5 × 107, or 3 × 107 plaque-forming units (PFU) of Prime-2-CoV_Beta on day 1 and a second dose on day 29. Here, we report safety and immunogenicity data collected up to 6 months after the first study vaccination. Prime-2-CoV_Beta is safe and well tolerated and elicits immune responses at higher dose levels in participants aged 18–55. A single dose of 3 × 107 PFU boosted binding and cross-neutralizing antibody responses that are maintained through 6 months after the first booster vaccination. Polyfunctional S-specific CD4+ and CD8+ T cell responses are observed after vaccination. No pre-existing or vaccine-induced neutralizing anti-vector antibodies are detected. Our findings highlight the potential of the ORFV vector as a safe platform for future vaccine design, which provides the ability to deliver multiple antigens and allows for repeat immunization.