SARS-CoV-2 BA.4 infection triggers more cross-reactive neutralizing antibodies than BA.1

Richardson, Simone I.; Motlou, Thopisang; Mescht, Mieke van der; Lambson, Bronwen E.; Everatt, Josie; Amoako, Daniel G.; Gottberg, Anne Van; Wolter, Nicole; Beer, Zelda de; Villiers, Talita Roma de; Bodenstein, Annie; Berg, Gretha van den; Rossouw, Theresa M.; Boswell, Michael T; Ueckermann, Veronica; Moore, Penny L.

doi:10.1101/2022.07.14.500039

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Here, we report that BA.4/BA.5 breakthrough infection of triple-mRNA vaccinated individuals is associated with robust neutralization of all currently or previously predominant Omicron VOCs, i.e., pan-Omicron neutralization. Our findings are consistent with a recent report showing strong cross-neutralization of Omicron BA.1, BA.2, Beta and Delta in sera from individuals vaccinated with BNT162b2 or an adenovirus-based vaccine and subsequent BA.4 breakthrough infection ( 28 ). In line with those observations in humans, we also found pan-Omicron neutralizing activity in sera of mice that received an Omicron BA.4/5 booster vaccine following primary immunization with BNT162b2, whereas an Omicron BA.1 boost induced lower levels of neutralizing antibody titers against BA.4/BA.5.…”

Section: Discussionsupporting

confidence: 93%

Exposure to BA.4/BA.5 Spike glycoprotein drives pan-Omicron neutralization in vaccine-experienced humans and mice

Muik

Lui

Bacher

et al. 2022

Preprint

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The SARS-CoV-2 Omicron variant and its sublineages show pronounced viral escape from neutralizing antibodies elicited by vaccination or prior SARS-CoV-2 variant infection owing to over 30 amino acid alterations within the spike (S) glycoprotein. We and others have recently reported that breakthrough infection of vaccinated individuals with Omicron sublineages BA.1 and BA.2 are associated with distinct patterns of cross-neutralizing activity against SARS-CoV-2 variants of concern (VOCs). BA.2 breakthrough infection mediated overall stronger cross-neutralization of BA.2 and its descendants (BA.2.12.1, BA.4, and BA.5) compared to BA.1 breakthrough infection. Here we characterized the effect of Omicron BA.4/BA.5 S glycoprotein exposure on the magnitude and breadth of the neutralizing antibody response upon breakthrough infection in vaccinated individuals and in mice upon booster vaccination. We show that immune sera from triple mRNA-vaccinated individuals with subsequent Omicron BA.4/BA.5 breakthrough infection display broad and robust neutralizing activity against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5. Administration of a prototypic BA.4/BA.5-adapted mRNA booster vaccine to mice following SARS-CoV-2 wild-type strain-based primary immunization is associated with similarly broad neutralizing activity. Immunization of naive mice with a bivalent mRNA vaccine (wild-type + Omicron BA.4/BA.5) induces strong and broad neutralizing activity against Omicron VOCs and previous variants. These findings suggest that when administered as boosters, mono- and bivalent Omicron BA.4/BA.5-adapted vaccines may enhance neutralization breadth, and in a bivalent format may also have the potential to confer protection to individuals with no pre-existing immunity against SARS-CoV-2.

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Section: Discussionsupporting

confidence: 93%

Exposure to BA.4/BA.5 Spike glycoprotein drives pan-Omicron neutralization in vaccine-experienced humans and mice

Muik

Lui

Bacher

et al. 2022

Preprint

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“…Here, we report that BA.4/BA.5 breakthrough infection of triple mRNA-vaccinated individuals is associated with robust neutralization of the previous Omicron variants BA.1, BA.2, BA.2.12.1, and BA.4/BA.5 itself. Our findings are consistent with a recent report showing strong cross-neutralization of Omicron BA.1, BA.2, Beta, and Delta in sera from individuals vaccinated with BNT162b2 or an adenovirus-based vaccine that encountered subsequent BA.4 breakthrough infection (24). In line with those observations in humans, we also found high GMTs against BA.4/5 and Omicron sublineage cross-neutralizing activity in sera of mice that were boosted with the monovalent Omicron BA.4/5-adapted vaccine after primary immunization with BNT162b2, whereas an Omicron BA.1 boost induced lower cross-neutralization of BA.4/5, BA.2, and BA.2.12.1.…”

Section: Discussionsupporting

confidence: 93%

Exposure to BA.4/5 S protein drives neutralization of Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 in vaccine-experienced humans and mice

et al. 2022

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The SARS-CoV-2 Omicron variant and its sublineages show pronounced viral escape from neutralizing antibodies elicited by vaccination or prior SARS-CoV-2 variant infection owing to over 30 amino acid alterations within the spike (S) glycoprotein. Breakthrough infection of vaccinated individuals with Omicron sublineages BA.1 and BA.2 is associated with distinct patterns of cross-neutralizing activity against SARS-CoV-2 variants of concern (VOCs). In continuation of our previous work, we characterized the effect of Omicron BA.4/BA.5 S glycoprotein exposure on the neutralizing antibody response upon breakthrough infection in vaccinated individuals and upon variant-adapted booster vaccination in mice. We found that immune sera from triple mRNA-vaccinated individuals with subsequent breakthrough infection during the Omicron BA.4/BA.5 wave showed cross-neutralizing activity against previous Omicron variants BA.1, BA.2, BA.2.12.1, and BA.4/BA.5 itself. Administration of a prototypic BA.4/BA.5-adapted mRNA booster vaccine to mice following SARS-CoV-2 wild-type strain-based primary immunization is associated with broader cross-neutralizing activity than a BA.1-adapted booster. While the Omicron BA-1-adapted mRNA vaccine in a bivalent format (wild-type + BA.1) broadens cross-neutralizing activity relative to the BA.1 monovalent booster, cross-neutralization of BA.2 and descendants is more effective in mice boosted with a bivalent wild-type + BA.4/BA.5 vaccine. In naïve mice primary immunization with the bivalent wild-type + Omicron BA.4/BA.5 vaccine induces strong cross-neutralizing activity against Omicron VOCs and previous variants. These findings suggest that when administered as boosters, mono- and bivalent Omicron BA.4/BA.5-adapted vaccines enhance neutralization breadth, and that the bivalent version also has the potential to confer protection to individuals with no pre-existing immunity against SARS-CoV-2.

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“…Seventeen studies analyzed the efficacy of CCP and VaxCCP against Omicron sublineages other than BA.1 (summarized in Table 2 ). Those studieslargely confirmed that Omicron CCP per se is poorly effective against the cognate or other Omicron sublineages 22 (with the lone exception of cross-reactions among lineages sharing L452 mutations 23 and broad-spectrum nAbs elicited by BA.5 24 ). On the contrary, both homologous and heterologous efficacy of Omicron VaxCCP is again universally preserved 15 , 25 .…”

Section: Resultsmentioning

confidence: 74%

Analysis of anti-Omicron neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

Focosi

Franchini

Joyner

et al. 2021

Preprint

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The novel SARS-CoV-2 Omicron variant of concern (VOCs), with its escape from unboosted vaccines and monoclonal antibodies, is demanding for a return to COVID19 convalescent plasma therapies. Lessons learnt from previous usage of CCP suggests focusing on outpatients and using high nAb-titer units in early disease stages. In this systematic analysis, we show that CCP from unvaccinated donors is not effective against Omicron, while CCP from vaccinees convalescents from previous VOCs or third-dose uninfected vaccinees is likely to remain effective against Omicron. countries. CCP remains the only antibody-based therapy that keeps up with the variants and provides an effective tool to combat the emergence of variants that defeat monoclonal antibodies. Consequently, there is a need for continue study of the variables that determine CCP efficacy.

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SARS-CoV-2 BA.4 infection triggers more cross-reactive neutralizing antibodies than BA.1

Cited by 4 publications

References 26 publications

Exposure to BA.4/BA.5 Spike glycoprotein drives pan-Omicron neutralization in vaccine-experienced humans and mice

Exposure to BA.4/BA.5 Spike glycoprotein drives pan-Omicron neutralization in vaccine-experienced humans and mice

Exposure to BA.4/5 S protein drives neutralization of Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 in vaccine-experienced humans and mice

Analysis of anti-Omicron neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

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