SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-weeks interval between doses

Continuous emergence of SARS-CoV-2 variants of concern (VOC) is fueling the COVID-19 pandemic. Omicron (B.1.1.529), is rapidly spreading worldwide. The large number of mutations in its Spike raised concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses was shown to elicit antibodies that efficiently recognize Spikes from different VOCs. Here we evaluated the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously-infected individuals that received their BNT162b2 mRNA vaccine 16-weeks apart. Omicron Spike was recognized less efficiently than D614G, Alpha, Beta, Gamma and Delta Spikes. We compared to plasma activity from participants receiving a short (4-weeks) interval regimen. Plasma from individuals of the long interval cohort neutralized better the Omicron Spike compared to those that received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.

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Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

PLoS Pathogens ◽

10.1371/journal.ppat.1010022 ◽

2021 ◽

Vol 17 (12) ◽

pp. e1010022

Author(s):

Chris Davis ◽

Nicola Logan ◽

Grace Tyson ◽

Richard Orton ◽

William T. Harvey ◽

...

Keyword(s):

South African ◽

Vaccine Efficacy ◽

Antigenic Drift ◽

Productive Infection ◽

Subsequent Reduction ◽

Fold Reduction ◽

Antibody Titres ◽

Efficacy Assessment ◽

Induced Immunity ◽

Over Time

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

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Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

10.1101/2021.06.23.21259327 ◽

2021 ◽

Author(s):

Chris Davis ◽

Nicola Logan ◽

Grace Tyson ◽

Richard Orton ◽

William Harvey ◽

...

Keyword(s):

South African ◽

Vaccine Efficacy ◽

Antigenic Drift ◽

Productive Infection ◽

Subsequent Reduction ◽

Fold Reduction ◽

Antibody Titres ◽

Efficacy Assessment ◽

Induced Immunity ◽

Over Time

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.1351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

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Host Factors Impact Vaccine Efficacy: Implications for Seasonal and Universal Influenza Vaccine Programs

Journal of Virology ◽

10.1128/jvi.00797-19 ◽

2019 ◽

Vol 93 (21) ◽

Cited By ~ 15

Author(s):

Santosh Dhakal ◽

Sabra L. Klein

Keyword(s):

Influenza Virus ◽

Influenza Vaccine ◽

Virus Vaccine ◽

Vaccine Efficacy ◽

Public Health Problem ◽

Influenza Virus Vaccine ◽

Host Factors ◽

Influenza Vaccines ◽

Vaccine Type ◽

Induced Immunity

ABSTRACT Influenza is a global public health problem. Current seasonal influenza vaccines have highly variable efficacy, and thus attempts to develop broadly protective universal influenza vaccines with durable protection are under way. While much attention is given to the virus-related factors contributing to inconsistent vaccine responses, host-associated factors are often neglected. Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of influenza virus vaccine efficacy. We hypothesize that host genetics, the hormonal milieu, and gut microbiota contribute to host-related differences in influenza virus vaccine efficacy. This review highlights the current insights and future perspectives into host-specific factors that impact influenza vaccine-induced immunity and protection. Consideration of the host factors that affect influenza vaccine-induced immunity might improve influenza vaccines by providing empirical evidence for optimizing or even personalizing vaccine type, dose, and use of adjuvants for current seasonal and future universal influenza vaccines.

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SARS-CoV-2 Convalescent Sera Binding and Neutralizing Antibody Concentrations Compared with COVID-19 Vaccine Efficacy Estimates Against Symptomatic Infection

10.1101/2021.11.24.21266812 ◽

2021 ◽

Author(s):

Amy J. Schuh ◽

Panayampalli S. Satheshkumar ◽

Stephanie Dietz ◽

Lara Bull-Otterson ◽

Myrna Charles ◽

...

Keyword(s):

Vaccine Efficacy ◽

Neutralizing Antibody ◽

Published Data ◽

Symptomatic Infection ◽

Convenience Sample ◽

Post Vaccination ◽

Antibody Assays ◽

Study Population ◽

Binding Antibody ◽

Induced Immunity

Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, ~88% of neutralizing and ~63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; ~30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19.

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Pertussis in England and Wales: an investigation of transmission dynamics and control by mass vaccination

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1989.0022 ◽

1989 ◽

Vol 236 (1284) ◽

pp. 213-252 ◽

Cited By ~ 48

Keyword(s):

Mathematical Models ◽

Vaccine Efficacy ◽

Case Reports ◽

Mass Vaccination ◽

Vaccine Uptake ◽

Transmission Dynamics ◽

England And Wales ◽

Epidemic Period ◽

The Impact ◽

Induced Immunity

The epidemiology of pertussis and its prospects for control by mass vaccination in England and Wales are investigated by analyses of longitudinal records on incidence and vaccine uptake, and horizontal data on age-stratified case reports. Mathematical models of the transmission dynamics of the infection that incorporate loss of natural and vaccine-induced immunity plus variable vaccine efficacy are developed, and their predictions compared with observed trends. Analyses of case reports reveal that the individual force of infection is age dependent, with peak transmission in the 5- to 10-year-old age class. A model incorporating this age dependency, along with partial vaccine efficacy and loss of vaccine-induced immunity, generates predicted patterns that best mirror observed trends since mass vaccination was inaugurated in 1957 in England and Wales. Model projections accurately mirror the failure of mass vaccination to increase the inter-epidemic period of the infection (three years) over that pertaining before control. The analysis suggests that this is due to the impact of partial vaccine efficacy. Projected trends to not accurately reflect the low levels of pertussis incidence reported between epidemics in the periods of high vaccine uptake. This is thought to arise from a combination of factors, including loss of natural and vaccine induced immunity, biases in case reporting (where reporting efficiency is positively associated with the incidence of pertussis), and seasonal variations in transmission. Model predictions suggest that the vaccination of 88% of each birth cohort before the age of 1 year will eliminate bacterial transmission, provided the vaccine confers lifelong protection against infection. If vaccine-induced immunity is significantly less than lifelong (or if vaccination fails to protect all its recipients) repeated cohort immunization is predicted to be necessary to eliminate transmission. Future research needs are discussed, and emphasis is placed on the need for more refined data on vaccine efficacy, the duration of natural and vaccine-induced immunity and the incidence of clinical pertussis and subclinical infections (perhaps by the development of reliable serological tests). Future mathematical models will need especially to incorporate seasonality in transmission.

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Measuring vaccine efficacy against infection and disease in clinical trials: sources and magnitude of bias in COVID-19 vaccine efficacy estimates

10.1101/2021.07.30.21260912 ◽

2021 ◽

Author(s):

Lucy R. Williams ◽

Neil M. Ferguson ◽

Christl A. Donnelly ◽

Nicholas C. Grassly

Keyword(s):

Vaccine Efficacy ◽

Asymptomatic Infection ◽

Phase Iii ◽

Uncertainty Interval ◽

Considerable Uncertainty ◽

Study Results ◽

Phase Iii Trials ◽

Asymptomatic Infections ◽

Protection Against Infection ◽

Induced Immunity

Background Phase III trials have estimated COVID-19 vaccine efficacy (VE) against symptomatic and asymptomatic infection. We explore the direction and magnitude of potential biases in these estimates and their implications for vaccine protection against infection and against disease in breakthrough infections. Methods We developed a mathematical model that accounts for natural and vaccine-induced immunity, changes in serostatus and imperfect sensitivity and specificity of tests for infection and antibodies. We estimated expected biases in VE against symptomatic, asymptomatic and any SARS-CoV-2 infections and against disease following infection for a range of vaccine characteristics and measurement approaches, and the likely overall biases for published trial results that included asymptomatic infections. Results VE against asymptomatic infection measured by PCR or serology is expected to be low or negative for vaccines that prevent disease but not infection. VE against any infection is overestimated when asymptomatic infections are less likely to be detected than symptomatic infections and the vaccine protects against symptom development. A competing bias towards underestimation arises for estimates based on tests with imperfect specificity, especially when testing is performed frequently. Our model indicates considerable uncertainty in Oxford-AstraZeneca ChAdOx1 and Janssen Ad26.COV2.S VE against any infection, with slightly higher than published, bias-adjusted values of 59.0% (95% uncertainty interval [UI] 38.4 to 77.1) and 70.9% (95% UI 49.8 to 80.7) respectively. Conclusion Multiple biases are likely to influence COVID-19 VE estimates, potentially explaining the observed difference between ChAdOx1 and Ad26.COV2.S vaccines. These biases should be considered when interpreting both efficacy and effectiveness study results.

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Full protection against all four SARS-CoV-2 variants of concern (VOC) in hamsters requires revision of spike antigen used for vaccination.

10.1101/2021.11.12.468374 ◽

2021 ◽

Author(s):

Sapna Sharma ◽

Thomas Vercruysse ◽

Lorena Sanchez-Felipe ◽

Winnie Kerstens ◽

Rana Abdelnabi ◽

...

Keyword(s):

First Generation ◽

Vaccine Candidate ◽

Marked Change ◽

Target Antigen ◽

Generation Vaccine ◽

Alpha Beta ◽

Antigenic Cartography ◽

Protection Against Infection ◽

Induced Immunity ◽

Full Protection

Current licensed COVID-19 vaccines are based on antigen sequences of initial SARS-CoV-2 isolates that emerged in 2019. By mid 2021 these historical virus strains have been completely replaced by new cosmopolitan SARS-CoV-2 lineages. The ongoing pandemic has been further driven by emerging variants of concern (VOC) Alpha, Beta, Gamma and, lately predominant, Delta. These are characterized by an increased transmissibility and possible escape from naturally acquired or vaccine-induced immunity. We here show, using a YF17D-vectored first-generation COVID-19 vaccine (Sanchez-Felipe et al., 2021) and a stringent hamster challenge model (Abdelnabi et al., 2021) that the immunity elicited by a prototypic spike antigen is insufficient to provide optimal protection against the Beta VoC, urging for an antigenic update. We therefore designed an updated second-generation vaccine candidate that carries the sequence of a spike antigen that includes crucial epitopes from multiple VOCs. This vaccine candidate yielded a marked change in target antigen spectrum covered as demonstrated by (i) antigenic cartography and (ii) full protection against infection and virus-induced disease caused by any of the four VOCs (Alpha, Beta, Gamma and Delta) used for challenge. This more universal COVID-19 vaccine candidate also efficiently blocked direct transmission of VOC Delta from vaccinated infected hamsters to non-vaccinated sentinels under prolonged co-housing conditions. In conclusion, our data suggest that current first-generation COVID-19 vaccines need to be adapted to cover emerging sequence diversity of VOC to preserve vaccine efficacy and to contain virus spread at the community level.

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Clinical and molecular epidemiology of influenza viruses from Romanian patients hospitalized during the 2019/20 season

PLoS ONE ◽

10.1371/journal.pone.0258798 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0258798

Author(s):

Victor Daniel Miron ◽

Leontina Bănică ◽

Oana Săndulescu ◽

Simona Paraschiv ◽

Marius Surleac ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Vaccine Efficacy ◽

Influenza A ◽

Influenza Viruses ◽

Antigenic Drift ◽

Epidemiological Surveillance ◽

Influenza B Virus ◽

Influenza B ◽

Equal Distribution ◽

B Lineage

Two main mechanisms contribute to the continuous evolution of influenza viruses: accumulation of mutations in the hemagglutinin and neuraminidase genes (antigenic drift) and genetic re-assortments (antigenic shift). Epidemiological surveillance is important in identifying new genetic variants of influenza viruses with potentially increased pathogenicity and transmissibility. In order to characterize the 2019/20 influenza epidemic in Romania, 1042 respiratory samples were collected from consecutive patients hospitalized with acute respiratory infections in the National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest Romania and tested for influenza A virus, influenza B virus and respiratory syncytial virus (RSV) by real-time PCR. Out of them, 516 cases were positive for influenza, with relatively equal distribution of influenza A and B. Two patients had influenza A and B co-infection and 8 patients had influenza-RSV co-infection. The most severe cases, requiring supplemental oxygen administration or intensive care, and the most deaths were reported in patients aged 65 years and over. Subtyping showed the predominance of A(H3N2) compared to A(H1N1)pdm09 pdm09 (60.4% and 39.6% of all subtyped influenza A isolates, respectively), and the circulation of Victoria B lineage only. Influenza B started to circulate first (week 47/2019), with influenza A appearing slightly later (week 50/2019), followed by continued co-circulation of A and B viruses throughout the season. Sixty-eight samples, selected to cover the entire influenza season and all circulating viral types, were analysed by next generation sequencing (NGS). All A(H1N1)pdm09 sequences identified during this season in Romania were clustered in the 6b1.A clade (sub-clades: 6b1.A.183P -5a and 6b1.A.187A). For most A(H1N1)pdm09 sequences, the dominant epitope was Sb (pepitope = 0.25), reducing the vaccine efficacy by approximately 60%. According to phylogenetic analysis, influenza A(H3N2) strains circulating in this season belonged predominantly to clade 3C.3A, with only few sequences in clade 3C.2A1b. These 3C.2A1b sequences, two of which belonged to vaccinated patients, harbored mutations in antigenic sites leading to potential reduction of vaccine efficacy. Phylogenetic analysis of influenza B, lineage Victoria, sequences showed that the circulating strains belonged to clade V1A3. As compared to the other viral types, fewer mutations were observed in B/Victoria strains, with limited impact on vaccine efficiency based on estimations.

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Vaccine-Induced Anti-Neuroblastoma Immunity Early after HSCT Arises in the Presence of Foxp3+CD25+CD4+ T Cells.

Blood ◽

10.1182/blood.v108.11.3692.3692 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3692-3692

Author(s):

Weiqing Jing ◽

Rimas J. Orentas ◽

Bryon D. Johnson

Keyword(s):

T Cells ◽

Adoptive Transfer ◽

Vaccine Efficacy ◽

Cd4 T Cells ◽

Cell Function ◽

Tumor Vaccine ◽

Neuroblastoma Cells ◽

Early Time ◽

Antibody Treatment ◽

Induced Immunity

Abstract Effective anti-neuroblastoma immunity can be induced in mice as early as 1 week after syngeneic HSCT by vaccination with neuroblastoma cells transfected to express CD80, CD86, CD54, and CD137L. However, effective vaccination at this early time point also requires adoptive transfer of T cells (2×107 splenocytes). Previous results in non-transplanted mice showed that T-reg depletion/blockade with anti-CD25 mAb (clone PC61) increased tumor vaccine efficacy. To determine if PC61 treatment might be effective early after HSCT, we first determined if CD4+CD25+Foxp3+ T-reg cells were present, derived either from host (i.e., they survived lethal TBI) or from the transferred spleen cells. Even though transferred splenocytes accelerated T cell reconstitution, HSCT recipient mice remained severely lymphopenic until 3 weeks after transplant. Furthermore, the percentage of Foxp3+ cells in the splenic CD4 fraction was significantly increased in transplanted mice, being as much as 3 times higher than that in non-transplanted mice (35% vs. 12%). During this time, the majority of CD25+Foxp3+CD4+ cells were derived from the adoptively-transferred T cells. Despite the presence of CD25+Foxp3+CD4+ T cells, protective anti-tumor immunity could still be efficiently induced. To examine whether depletion/inhibition of CD25+ T-reg cells could further enhance vaccine-induced immunity in transplanted mice, two strategies were tested: (a) physical depletion of CD25+ regulatory T cells from the adoptively-transferred T cells, and (b) anti-CD25 mAb treatment of the transplanted mice 4 days after HSCT to target both transferred and residual endogenous CD25+ cells. Immunomagnetic depletion eliminated more then 95% of the CD25+ T cells in the transferred population, but only 70% of Foxp3+CD4+ T cells. Adoptive transfer of CD25-depleted splenocytes at the time of HSCT resulted in modest increased tumor vaccine efficacy as compared to mice given non-depleted splenocytes. Two weeks after HSCT, both groups of mice contained similar percentages of Foxp3+CD4+ T cells in the blood and lymph nodes, but a lower frequency of Foxp3+CD4+ T cells was detected in the spleens of mice given CD25-depleted splenocytes (35% vs. 43%, p<0.01). Our second strategy, treatment of HSCT recipients with anti-CD25 mAb prior to tumor vaccination, negatively influenced the vaccine-induced anti-tumor response and resulted in decreased survival. This suggested that the antibody treatment inhibited effector cell function in the early post-transplant setting. IFN-γ ELISpot analysis demonstrated that vaccinated transplant recipients given anti-CD25 mAb had significantly decreased numbers of tumor-specific CD4 T cells in spleen. Collectively, these results suggest that anti-neuroblastoma immunity could be induced in the present of CD25+Foxp3+CD4+ T-reg cells early after HSCT; strategies that targeted at CD25 did not significantly increase the efficacy of the tumor vaccine.

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Covid-19 disease dynamics with vaccination: The effect of uncertainty

10.1101/2022.01.10.22269006 ◽

2022 ◽

Author(s):

Nandadulal Bairagi ◽

Abhijiit Majumder

Keyword(s):

Mathematical Models ◽

Vaccine Efficacy ◽

Loss Rate ◽

Vaccination Rate ◽

Model Parameters ◽

Extinction Time ◽

Disease Eradication ◽

Average Value ◽

Force Of Infection ◽

Induced Immunity

Rate parameters are critical in estimating the covid burden using mathematical models. In the Covid-19 mathematical models, these parameters are assumed to be constant. However, uncertainties in these rate parameters are almost inevitable. In this paper, we study a stochastic epidemic model of the SARS-CoV-2 virus infection in the presence of vaccination in which some parameters fluctuate around its average value. Our analysis shows that if the stochastic basic reproduction number (SBRN) of the system is greater than unity, then there is a stationary distribution, implying the long-time disease persistence. A sufficient condition for disease eradication is also prescribed for which the exposed class goes extinct, followed by the infected class. The disease eradication criterion may not hold if the rate of vaccine-induced immunity loss increases or/and the force of infection increases. Using the Indian Covid-19 data, we estimated the model parameters and showed the future disease progression in the presence of vaccination. The disease extinction time is estimated under various conditions. It is revealed that the mean extinction time is an increasing function of both the force of infection and immunity loss rate and shows the lognormal distribution. We point out that disease eradication might not be possible even at a higher vaccination rate if the vaccine-induced immunity loss rate is high. Our observation thus indicates the endemicity of the disease for the existing vaccine efficacy. The disease eradication is possible only with a higher vaccine efficacy or a reduced infection rate.

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