SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines

Shen, Xiaoying; Tang, Haili; McDanal, Charlene; Wagh, Kshitij; Fischer, Will; Theiler, James; Yoon, Hyejin; Li, Dapeng; Haynes, Barton F.; Sanders, Kevin O.; Gnanakaran, S.; Hengartner, Nick; Pajón, Rolando; Smith, Gale; Glenn, Gregory M.; Korber, Bette; Montefiori, David C.

doi:10.1016/j.chom.2021.03.002

Cited by 320 publications

(212 citation statements)

References 55 publications

(58 reference statements)

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“…Unfortunately, data for the RNA-based vaccines against RBD antigen were not available after the first dose. Protection against variants has been shown with the mRNA-based vaccine against the United Kingdom (B.1.1.7, also called 20I/501Y.V1) variant [ 44 , 45 ], but they may be less effective against the variant first detected in South Africa (B.1.351, known as 20H/501Y.V2) [ 46 ]. A week after the second dose of mRNA-based vaccine, induction of neutralizing antibody titers in the serum sample was 6-fold lower for participants bearing B.1.351 variant compared to original Wuhan-Hu-1 spike protein [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Zarei²,

et al. 2021

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The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936–0.954) and 80.2% (95% CI 0.96.4–0.92.7) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6%; 95% CI 0.939–0.997) and second (98.2%; 95% CI 0.980–0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines’ adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Zarei²,

et al. 2021

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“…We also examined the presence of escape mutations for each antibody class in some key emerging viral lineages ( Figure 6C ). All these emerging viral lineages except B.1.1.7 14,16,[39][40][41] have a mutation that escapes some antibodies from at least one class. The class 2 antibody escape mutation E484K is present in the B.1.351, P.1, P.2 and B.1.526 lineages ( Figure 6C ) 1,2,[4][5][6] .…”

Section: Mutations That Reduce Binding By Class 1 and 2 Antibodies Armentioning

confidence: 99%

Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies

Greaney

Starr

Barnes

et al. 2021

Preprint

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Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasma, including plasma from individuals from whom some of the antibodies were isolated. The plasma-escape maps most closely resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is dominated by a single class of antibodies targeting an epitope that is already undergoing rapid evolution.

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“…Mutations found in emergent S variants decrease sensitivity to neutralization by mAbs, convalescent plasma, and sera from vaccinated individuals (27,37,58,(61)(62)(63)(64)(65)(66)(67)(68)(69)(70). As a result, there is concern that these and other emerging variants can evade neutralizing antibody responses generated during infection with variants circulating earlier in the pandemic and also from neutralizing antibody responses elicited by vaccines based on the spike protein of the Wuhan-Hu-1 variant.…”

mentioning

confidence: 99%

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Stamatatos

Czartoski

Wan

et al. 2021

Science

540

121

492

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Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naïve donors collected prior to, and following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 and B.1.351 variants. Pre-vaccination sera from recovered donors neutralized Wuhan-Hu-1 and sporadically neutralized B.1.351, but a single immunization boosted neutralizing titers against all variants and SARS-CoV-1 by up to 1000-fold. Neutralization was due to antibodies targeting the receptor binding domain and was not boosted by a second immunization. Immunization of naïve donors also elicited cross-neutralizing responses, but at lower titers. Our study highlights the importance of vaccinating both uninfected and previously infected persons to elicit cross-variant neutralizing antibodies.

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SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines

Abstract: Highlights d B.1.1.7 is not a neutralization escape variant of concern for COVID-19 vaccines d B.1.1.7 is unlikely to increase the risk of SARS-CoV-2 reinfection d B.1.1.7 escapes a subset of RBD-specific antibodies

Cited by 320 publications

References 55 publications

Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

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