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Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity.

ABSTRACT: Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Crossneutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.

SUBMITTER: Garcia-Beltran WF

PROVIDER: S-EPMC7899476 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity.

Project description:Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.

| S-EPMC7953441 | biostudies-literature

Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.

Project description:Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.

| S-EPMC10942518 | biostudies-literature

Evasion of vaccine-induced humoral immunity by emerging sub-variants of SARS-CoV-2.

Project description:Background: Emergence of vaccine-escaping SARS-CoV-2 variants is a serious problem for global public health. The currently rampant Omicron has been shown to possess remarkable vaccine escape; however, the selection pressure exerted by vaccines might pave the way for other escape mutants in the near future. Materials & methods: For detection of neutralizing antibodies, the authors used the recently developed HiBiT-based virus-like particle neutralization test system. Sera after vaccination (two doses of Pfizer/BioNTech mRNA vaccine) were used to evaluate the neutralizing activity against various strains of SARS-CoV-2. Results: Beta+R346K, which was identified in the Philippines in August 2021, exhibited the highest vaccine resistance among the tested mutants. Surprisingly, Mu+K417N mutant exhibited almost no decrease in neutralization. Imdevimab retained efficacy against these strains. Conclusions: Mutations outside the receptor-binding domain contributed to vaccine escape. Both genomic surveillance and phenotypic analysis synergistically accelerate identifications of vaccine-escaping strains.

| S-EPMC8966691 | biostudies-literature

Investigation of SARS-CoV-2 variants that escape from cellular immunity in the absence of humoral immunity

Project description:X-linked agammaglobulinemia (XLA) is a primary immunodeficiency causing a lack of immunoglobulin production. A COVID-19 patient with XLA showed persistent infection for more than 239 days, representing the longest duration yet reported, in whom SARS-CoV-2 evolved increased proliferative capacity. We identify a mutation of SARS-CoV-2 that is responsible for the immune escape from the cellular immunity of this patient, as well as the TCR that could recognize the wild type antigen but not the correspoinding mutant antigen.

2023-05-12 | GSE190895 | GEO

Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.

Project description:Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens. Ligand attachment via a covalent bond was achieved using a protein superglue, DogTag/DogCatcher (similar to SpyTag/SpyCatcher), in a rapid and spontaneous reaction requiring only co-incubation of ligand and vector components. DogTag was inserted into surface-exposed loops in the adenovirus hexon protein to allow attachment of DogCatcher-fused ligands on virus particles. Efficient coverage of the capsid surface was achieved using various ligands, with vector infectivity retained in each case. Capsid decoration shielded particles from vector neutralizing antibodies. In prime-boost regimens, adenovirus vectors decorated with the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike induced >10-fold higher SARS-CoV-2 neutralization titers compared with an undecorated vector encoding spike. Importantly, decorated vectors achieved equivalent or superior T cell immunogenicity against encoded antigens compared with undecorated vectors. We propose capsid decoration using protein superglues as a novel strategy to improve efficacy and boostability of adenovirus-based vaccines and therapeutics.

| S-EPMC9364715 | biostudies-literature

Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity.

Project description:The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1-6. Here we analysed the development of anti-SARS-CoV-2 antibody and T cell responses in individuals who were previously infected (recovered) or uninfected (naive) and received mRNA vaccines to SARS-CoV-2. While individuals who were previously infected sustained higher antibody titres than individuals who were uninfected post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (for example, B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (for example, B.1.617.2). While both groups retained neutralization capacity against all variants, plasma from individuals who were previously infected and vaccinated displayed overall better neutralization capacity than plasma from individuals who were uninfected and also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the effect of emerging variants on antibody neutralizing activity.

| S-EPMC9348899 | biostudies-literature

Neutralization of alpha, gamma, and D614G SARS-CoV-2 variants by CoronaVac vaccine-induced antibodies.

Project description:Vaccination generates a neutralizing immune response against SARS-CoV-2. The genomic surveillance is showing the emergence of variants with mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we report the neutralization potency against alpha, gamma, and D614G SARS-CoV-2 variants in 44 individuals that received two doses of CoronaVac vaccine, an inactivated SARS-CoV-2 vaccine. Plasma samples collected at 60 days after the second dose of CoronaVac were analyzed by the reduction of cytopathic effect in Vero E6 cells with the three infectious variants of SARS-CoV-2. Plasma showed lower neutralization with alpha (geometric mean titer [GMT] = 18.5) and gamma (GMT = 10.0) variants than with D614G (GMT = 75.1) variant. Efficient neutralization against the alpha and gamma variants was not detected in 31.8% and 59.1% of plasma, respectively. These findings suggest the alpha and gamma variants could escape from neutralization by antibodies elicited by vaccination. Robust genomic and biological surveillance of viral variants could help to develop effective strategies for the control of SARS-CoV-2.

| S-EPMC8662277 | biostudies-literature

Broad neutralization against SARS-CoV-2 variants induced by a next-generation protein vaccine V-01.

Project description: Not available

| S-EPMC8630016 | biostudies-literature

Humoral immunity for durable control of SARS-CoV-2 and its variants.

Project description:The coronavirus disease 2019 (COVID-19) pandemic is ongoing because of the repeated emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, highlighting the importance of developing vaccines for variants that may continue to emerge. In the present review, we discuss humoral immune responses against SARS-CoV-2 with a focus on the antibody breadth to the variants. Recent studies have revealed that the temporal maturation of humoral immunity improves the antibody potency and breadth to the variants after infection or vaccination. Repeated vaccination or infection further accelerates the expansion of the antibody breadth. Memory B cells play a central role in this phenomenon, as the reactivity of the B-cell antigen receptor (BCR) on memory B cells is a key determinant of the antibody potency and breadth recalled upon vaccination or infection. The evolution of memory B cells remarkably improves the reactivity of BCR to antigenically distinct Omicron variants, to which the host has never been exposed. Thus, the evolution of memory B cells toward the variants constitutes an immunological basis for the durable and broad control of SARS-CoV-2 variants.

| S-EPMC9834039 | biostudies-literature

Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants.

Project description:The first-generation COVID-19 vaccines have been effective in mitigating severe illness and hospitalization, but recurring waves of infections are associated with the emergence of SARS-CoV-2 variants that display progressive abilities to evade antibodies, leading to diminished vaccine effectiveness. The lack of clarity on the extent to which vaccine-elicited mucosal or systemic memory T cells protect against such antibody-evasive SARS-CoV-2 variants remains a critical knowledge gap in our quest for broadly protective vaccines. Using adjuvanted spike protein–based vaccines that elicit potent T cell responses, we assessed whether systemic or lung-resident CD4 and CD8 T cells protected against SARS-CoV-2 variants in the presence or absence of virus-neutralizing antibodies. We found that 1) mucosal or parenteral immunization led to effective viral control and protected against lung pathology with or without neutralizing antibodies, 2) protection afforded by mucosal memory CD8 T cells was largely redundant in the presence of antibodies that effectively neutralized the challenge virus, and 3) “unhelped” mucosal memory CD8 T cells provided no protection against the homologous SARS-CoV-2 without CD4 T cells and neutralizing antibodies. Significantly, however, in the absence of detectable virus-neutralizing antibodies, systemic or lung-resident memory CD4 and “helped” CD8 T cells provided effective protection against the relatively antibody-resistant B1.351 (β) variant, without lung immunopathology. Thus, induction of systemic and mucosal memory T cells directed against conserved epitopes might be an effective strategy to protect against SARS-CoV-2 variants that evade neutralizing antibodies. Mechanistic insights from this work have significant implications in the development of T cell–targeted immunomodulation or broadly protective SARS-CoV-2 vaccines.

| S-EPMC9171754 | biostudies-literature

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