Previously infected vaccinees broadly neutralize SARS-CoV-2 variants

Leier, Hans C.; Bates, Timothy A.; Lyski, Zoë L; McBride, Savannah K.; Lee, David X; Coulter, Felicity J; Goodman, James R.; Lu, Zhengchun; Curlin, Marcel E.; Messer, William B.; Tafesse, Fikadu G.

doi:10.1101/2021.04.25.21256049

Cited by 17 publications

(13 citation statements)

References 22 publications

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“…Sera from infected-vaccinated donors showed greater breadth of neutralization and more effective neutralization of VOCs than sera from donors who were only previously infected or only vaccinated. Consistent with previous studies, neutralization efficacy of infected-vaccinated sera against VOCs was similar to that against the ancestral strain of SARS-CoV-2 12,43,48,49 (Fig. 1c).…”

Section: Resultssupporting

confidence: 91%

Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses

Musharrafieh

Song

et al. 2021

Preprint

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The emergence of current SARS-CoV-2 variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed. Notably, several recent studies have revealed that vaccination of recovered COVID-19 donors results in enhanced nAb responses compared to SARS-CoV-2 infection or vaccination alone. Here, we utilized a targeted donor selection strategy to isolate a large panel of broadly neutralizing antibodies (bnAbs) to sarbecoviruses from two such donors. Many of the bnAbs are remarkably effective in neutralization against sarbecoviruses that use ACE2 for viral entry and also show strong binding to non-ACE2-using sarbecoviruses. The bnAbs are equally effective against SARS-CoV-2 VOCs compared to the original virus. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor binding domain (RBD) as opposed to strain-specific nAbs to the receptor binding site that are commonly elicited in SARS-CoV-2 infection and vaccination. The generation of a large panel of potent bnAbs provides new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and, importantly, provides a basis for effective design of pan-sarbecovirus vaccines.

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Section: Resultssupporting

confidence: 91%

Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses

Musharrafieh

Song

et al. 2021

Preprint

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“…Several studies have compared neutralising antibody responses after vaccination of previously infected individuals with those of naive individuals. 26 , 27 , 28 , 29 , 30 These studies have found that vaccination with a single dose of mRNA vaccine is sufficient to boost responses in previously infected individuals (and indeed a second dose has minimal effect). 28 , 29 Aggregating these studies, we found that vaccination of convalescent individuals led to 2–10-fold higher neutralisation titres than that seen in naive individuals after primary vaccination ( figure 3 ; appendix p 19 ) 26 , 27 , 28 , 29 , 30 , 31 and improved cross-reactivity to variants.…”

Section: Resultsmentioning

confidence: 99%

“… 26 , 27 , 28 , 29 , 30 These studies have found that vaccination with a single dose of mRNA vaccine is sufficient to boost responses in previously infected individuals (and indeed a second dose has minimal effect). 28 , 29 Aggregating these studies, we found that vaccination of convalescent individuals led to 2–10-fold higher neutralisation titres than that seen in naive individuals after primary vaccination ( figure 3 ; appendix p 19 ) 26 , 27 , 28 , 29 , 30 , 31 and improved cross-reactivity to variants. 27 , 28 , 29 , 30 Although increases varied between studies, vaccination of convalescent individuals with mRNA vaccines led to boosting of normalised neutralisation titres to 12-fold (range 6–29) higher than that seen in early convalescence (and higher than that seen in any current vaccination regimen; figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis

et al. 2022

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“…There are reports 58 of the development of adequate neutralizing antibodies against SARS-CoV-2 variants following administration of the existing mRNA vaccines to previously infected subjects.…”

Section: Discussionmentioning

confidence: 99%

“…The effectiveness of the neutralizing antibodies developed against B.1.1.7 and B.1.351 variants in those who received a BNT162b2 mRNA vaccine, have been reported as 90% and 75%, respectively 57 . There are reports 58 of the development of adequate neutralizing antibodies against SARS-CoV-2 variants following administration of the existing mRNA vaccines to previously infected subjects. However, our data suggests that as the immune response to SARS-CoV-2 spike antigen matures in vaccinated subjects, susceptibility to the variants will remain significant, raising the question if variant-focused re-vaccination with modified vaccines will become necessary?…”

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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Previously infected vaccinees broadly neutralize SARS-CoV-2 variants

Cited by 17 publications

References 22 publications

Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses

Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses

Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis

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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