Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant

Edara, Venkata Viswanadh; Norwood, Carson; Floyd, Katharine; Lai, Lilin; Davis-Gardner, Meredith E.; Hudson, William Henry; Mantus, Grace; Nyhoff, Lindsay E.; Adelman, Max W.; Fineman, Rebecca; Patel, Shivan; Byram, Rebecca; Gomes, Dumingu Nipuni; Garett, Michael; Abdullahi, Hayatu; Beydoun, Nour; Panganiban, Bernadine; McNair, Nina; Hellmeister, Kieffer; Pitts, Jamila; Winters, Joy; Kleinhenz, Jennifer M.; Usher, Jacob; Piantadosi, Anne; Waggoner, Jesse J.; Babiker, Ahmed; Stephens, David S.; Anderson, Evan J.; Edupuganti, Srilatha; Rouphael, Nadine; Ahmed, Rafi; Wrammert, Jens; Suthar, Mehul S.

doi:10.1101/2021.02.20.432046

Cited by 37 publications

(30 citation statements)

References 34 publications

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“…If the number of positive safety reports were to be increased in the coming months, one could expect that anxiety and fear towards adverse event would decrease. Other components such as efficacy, and length of immunization, would become more relevant, especially in light of the emergence of variants of concerns and recombining viruses [39,40]. Most (60%) professionals were hesitant towards vaccination.…”

Section: Discussionmentioning

confidence: 99%

Hesitancy towards COVID-19 Vaccination among Healthcare Workers: A Multi-Centric Survey in France

et al. 2021

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Vaccination programs against COVID-19 are being scaled up. We aimed to assess the effects of vaccine characteristics on vaccine hesitancy among healthcare workers in a multi-center survey conducted within French healthcare facilities from 1 December 2020 to 26 March 2021. We invited any healthcare workers naïve of COVID-19 vaccination to complete an online self-questionnaire. They reported on their socio-demographic characteristics, as well as their perception and beliefs towards vaccination. We measured their willingness to get vaccinated in eight scenarios for candidates’ vaccines presented sequentially (1 to 4-point scale). Candidates’ vaccines varied for efficacy (25%, 50%, 100%), length of immunization (1 year or lifetime), frequency (<1/100, <1/10,000), and severity (none, moderate, severe) of adverse events. We analyzed 4349 healthcare workers’ responses with interpretable questionnaires. The crude willingness to get vaccinated was 53.2% and increased over time. We clustered the trajectories of responses using an unsupervised classification algorithm (k-means) and identified four groups of healthcare workers: those willing to get vaccinated in any scenario (18%), those not willing to get vaccinated at all (22%), and those hesitating but more likely to accept (32%) or reject (28%) the vaccination depending on the scenario. In these last two subgroups, vaccine acceptance was growing with age, educational background and was higher among men with condition. Compared to an ideal vaccine candidate, a 50% reduced efficacy resulted in an average drop in acceptance by 0.8 (SD ± 0.8, −23.5%), while it was ranging from 1.4 (SD ± 1.0, −38.4%) to 2.1 (SD ± 1.0, −58.4%) in case of severe but rare adverse event. The acceptance of a mandatory immunization program was 29.6% overall and was positively correlated to the willingness to get vaccinated, ranging from 2.4% to 60.0%. Even if healthcare workers represent a heterogeneous population, most (80%) could accept the vaccination against COVID-19. Their willingness to get the vaccine increased over time and as immunization programs became available. Among hesitant professionals, the fear of adverse events was the main concern. Targeted information campaigns reassuring about adverse events may increase vaccine coverage, in a population with a strong opinion about mandatory immunization programs.

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Section: Discussionmentioning

confidence: 99%

Hesitancy towards COVID-19 Vaccination among Healthcare Workers: A Multi-Centric Survey in France

et al. 2021

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“…SARS-CoV-2 is an enveloped, positive-sense, singlestranded RNA beta-coronavirus, being prone to mutate very rapidly, since during RNA replication no error-correction mechanisms is used when copying the RNA genetic information into DNA [25][26][27][28]. Such mutations can confer new features to the virus, including the ability to infect new types of cells, or even new organisms and thus to determine the spillover, and this phenomenon occurred extensively in the case of SARS-CoV-2, as already mentioned here [11][12][13]. Like the preceding two CoVs that provoked outbreaks, SARS-CoV and MERS-CoV, the genome of SARS-CoV-2 encodes for several non-structural proteins (nsps), including several enzymes, such as an RNA-dependent RNA polymerase (RdRp), a helicase, a 3-chymotrypsin-like protease, also known as main protease (MPro) and a papain-like protease (PLP).…”

Section: Coronavirusesmentioning

confidence: 89%

“…The monoclonal antibodies (MAbs) constitute another therapeutic approach that is being pursued, with some highly effective ones discovered from plasma of convalescent COVID-19 patients, now in clinical trials [11]. However, although vaccines and MAbs already showed their efficacy and will definitely be useful to stop or at least slow down the pandemic, the continuous evolution of the virus, which uses a variety of immune escape mechanisms, will probably lead to the emergence of variants which are not neutralized by these agents, as already reported for the South African and Brazilian SARS-CoV-2 strains [12,13]. For these reasons, novel small molecule antiviral drugs capable of impairing the replication of CoV that can be used in the current outbreak and maybe also in future occurrences, are in exceedingly high demand but are scarcely available to date [14].…”

Section: Coronavirusesmentioning

confidence: 98%

Coronaviruses

Supuran

2021

Expert Opinion on Therapeutic Patents

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“…SARS-CoV-2 strain analysis in participants in Phase 3 studies in South Africa has revealed that some vaccines show diminished protection against the B.1.351 variant strain, 17 including ChAdOx, 18 NVX-CoV2373, 19,20 and Ad26.COV2-S. 21 In addition, in vitro studies show that wild type S-specific antibodies elicited by mRNA-1273 and BNT162b1 show reduced binding to the B.1.351 variant S protein. [22][23][24] Taken together, these findings raise the concern that monovalent vaccines targeting only the S protein may not be the most optimal strategy for conferring protection against continually emerging variants. SARS-CoV-2 expresses a number of other immunogenic proteins that may induce protective antibody and/or T cell responses.…”

Section: Introductionmentioning

confidence: 99%

Prime hAd5 Spike + Nucleocapsid Vaccination Induces Ten-Fold Increases in Mean T-Cell Responses in Phase 1 Subjects that are Sustained Against Spike Variants

Sieling

King

Wong

et al. 2021

Preprint

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In response to the need for a safe, efficacious vaccine that provides broad immune protection against SARS-CoV-2 infection, we have developed a dual-antigen COVID-19 vaccine. The vaccine delivers both the viral spike (S) protein modified to increase cell-surface expression (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to enhance MHC class I and II presentation and T-cell responses. The vaccine antigens are delivered using a human adenovirus serotype 5 (hAd5) platform with E1, E2b, and E3 regions deleted that has been shown in previous cancer vaccine studies to be effective in the presence of pre-existing hAd5 immunity. Here, we demonstrate the hAd5 S-Fusion + N-ETSD (hAd5 S + N) vaccine antigens when expressed by dendritic cells (DCs) of previously SARS-CoV-2-infected patients elicit Th1 dominant activation of autologous patient T cells, indicating the vaccine antigens have the potential for generating immune responses in patients previously infected or vaccinated. We further demonstrate that participants in our open-label Phase 1b study of the dual-antigen hAd5 S + N vaccine generate Th1 dominant S- and N-specific T cells after a single prime subcutaneous injection and that the magnitude of these responses were comparable to those seen for T cells from previously infected patients. We further present our in silico prediction of T-cell epitope HLA binding for both the first-wave SARS-CoV-2 ‘A’ strain and the K417N, E484K, and N501Y S as well as the T201I N variants that suggests T-cell responses to the hAd5 S + N vaccine will retain efficacy against these variants. These findings that the dual-antigen hAd5 S + N vaccine elicits SARS-CoV-2-relevant T-cell responses and that such cell-mediated protection is likely to be sustained against emerging variants supports the testing of this vaccine as a universal booster that would enhance and broaden existing immune protection conferred by currently approved S-based vaccines.

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Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant

Cited by 37 publications

References 34 publications

Hesitancy towards COVID-19 Vaccination among Healthcare Workers: A Multi-Centric Survey in France

Hesitancy towards COVID-19 Vaccination among Healthcare Workers: A Multi-Centric Survey in France

Coronaviruses

Prime hAd5 Spike + Nucleocapsid Vaccination Induces Ten-Fold Increases in Mean T-Cell Responses in Phase 1 Subjects that are Sustained Against Spike Variants

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