Cross-Reactive Neutralizing Antibody Responses Elicited by SARS-CoV-2 501Y.V2 (B.1.351)

Moyo-Gwete, Thandeka; Madzivhandila, Mashudu; Makhado, Zanele; Ayres, Frances; Mhlanga, Donald; Oosthuysen, Brent; Lambson, Bronwen E.; Kgagudi, Prudence; Tegally, Houriiyah; Iranzadeh, Arash; Doolabh, Deelan; Tyers, Lynn; Chinhoyi, Lionel; Mennen, Mathilda; Skelem, Sango; Marais, Gert; Wibmer, Constantinos Kurt; Bhiman, Jinal N.; Ueckermann, Veronica; Rossouw, Theresa M.; Boswell, Michael T; Oliveira, Túlio de; Williamson, Carolyn; Burgers, Wendy A.; Ntusi, Ntobeko; Morris, Lynn; Moore, Penny L.

doi:10.1056/nejmc2104192

Cited by 123 publications

(139 citation statements)

References 4 publications

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“…In this study, we demonstrate that infection with the B.1.351 variant results in robust T cell responses, comparable to responses elicited to ancestral strains. This work extends our recent findings on neutralizing antibody responses elicited by B.1.351 (25). We also demonstrate for the first time that the recognition of epitopes by CD4 T cells targeting variable spike regions was affected by B.1.351 spike mutations in patients infected with ancestral lineages.…”

Section: Discussionsupporting

confidence: 88%

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Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity

Riou

Keeton

Moyo-Gwete

et al. 2021

Preprint

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SARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (first wave), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5%) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3/44) mounted CD8 responses that targeted the mutated regions. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease.

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Section: Discussionsupporting

confidence: 88%

“…Sequencing was performed as previously published (25). Briefly, cDNA was synthesized from RNA extracted from the nasopharyngeal swabs using the Superscript IV First Strand synthesis system (Life Technologies, Carlsbad, CA) and random hexamer primers.…”

Section: Sars-cov-2 Spike Whole Genome Sequencingmentioning

confidence: 99%

Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity

Riou

Keeton

Moyo-Gwete

et al. 2021

Preprint

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“…Overall, our findings provide important evidence for broad and potent neutralizing antibody responses against emerging SARS-CoV-2 variants, even with exposure to only wildtype SARS-CoV-2 antigen. This reinforces a recent report that natural infection with B.1.351 elicits a similar cross-reactive neutralizing antibody response against B.1.351, P.1, and original SARS-CoV-2 18 . While these and other laboratory results must be validated by ongoing population-level studies, they indicate a novel role for COVID-19 vaccines in protecting hard-hit populations from future waves of the pandemic.…”

Section: Mainsupporting

confidence: 91%

Previously infected vaccinees broadly neutralize SARS-CoV-2 variants

Leier

Bates

Lyski

et al. 2021

Preprint

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We compared the serum neutralizing antibody titers before and after two doses of the BNT162b2 COVID-19 vaccine in ten individuals who recovered from SARS-CoV-2 infection prior to vaccination to 20 individuals with no history of infection, against clinical isolates of B.1.1.7, B.1.351, P.1, and the original SARS-CoV-2 virus. Vaccination boosted pre-existing levels of anti-SARS-CoV-2 spike antibodies 10-fold in previously infected individuals, but not to levels significantly higher than those of uninfected vaccinees. However, neutralizing antibody titers increased in previously infected vaccinees relative to uninfected vaccinees against every variant tested: 5.2-fold against B.1.1.7, 6.5-fold against B.1.351, 4.3-fold against P.1, and 3.4-fold against original SARS-CoV-2. Our study indicates that a first-generation COVID-19 vaccine provides broad protection from SARS-CoV-2 variants in individuals with previous infection.

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“…There are concerns 55,59 regarding potential problems with the effectiveness of such modified vaccines; however, there are not at present, strong reasons to think that the current vaccine regimen, or repeated doses of the existing vaccines, are likely to induce BNABs against SARS-CoV-2 variants. By contrast, a potent crossreactive antibody 60 derived from a SARS-CoV-2-variant epitope has recently been reported, suggesting that modified vaccines produced in this fashion may prove more broadly effective. Widely administered booster immunizations against reference/variants will expose a previously vaccinated and sensitized population to risk of vaccine reaction with attendant risks and discomforts 61 .…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Strain-specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

Narowski

Raphel

Adams

et al. 2021

Preprint

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With the advance of SARS-CoV-2 vaccines, the outlook for overcoming the global COVID-19 pandemic has improved. However, understanding of immunity and protection offered by the SARS-CoV-2 vaccines against circulating variants of concern (VOC) is rapidly evolving. We investigated the mRNA vaccine-induced antibody responses against the referent WIV04 (Wuhan) strain, circulating variants, and human endemic coronaviruses in 168 naive and previously infected people at three-time points. Samples were collected prior to vaccination, after the first and after the second doses of one of the two available mRNA-based vaccines. After full vaccination, both naive and previously infected participants developed comparable robust SARS-CoV-2 specific spike IgG levels, modest IgM and IgA binding antibodies, and varying degrees of HCoV cross-reactive antibodies. However, the strength and frequency of neutralizing antibodies produced in naive people were significantly lower than in the previously infected group. We also found that 1/3rd of previously infected people had undetectable neutralizing antibodies after the first vaccine dose; 40% of this group developed neutralizing antibodies after the second dose. In all subjects neutralizing antibodies produced against the B.1.351 and P.1 variants were weaker than those produced against the reference and B.1.1.7 strains. Our findings provide support for future booster vaccinations modified to be active against the circulating variants.

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Cross-Reactive Neutralizing Antibody Responses Elicited by SARS-CoV-2 501Y.V2 (B.1.351)

Cited by 123 publications

References 4 publications

Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity

Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity

Previously infected vaccinees broadly neutralize SARS-CoV-2 variants

SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Strain-specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

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