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Circulating neutralizing antibodies and SARS-CoV-2 variant replication following postvaccination infections
Miguel A. Garcia-Knight, J. Daniel Kelly, Scott Lu, Michel Tassetto, Sarah A. Goldberg, Amethyst Zhang, Jesus Pineda-Ramirez, Khamal Anglin, Michelle C. Davidson, Jessica Y. Chen, Maya Fortes-Cobby, Sara Park, Ana Martinez, Matthew So, Aidan Donovan, Badri Viswanathan, Eugene T. Richardson, David R. McIlwain, Brice Gaudilliere, Rachel L. Rutishauser, Ahmed Chenna, Christos Petropoulos, Terri Wrin, Steven G. Deeks, Glen R. Abedi, Sharon Saydah, Jeffrey N. Martin, Melissa Briggs Hagen, Claire M. Midgley, Michael J. Peluso, Raul Andino
Miguel A. Garcia-Knight, J. Daniel Kelly, Scott Lu, Michel Tassetto, Sarah A. Goldberg, Amethyst Zhang, Jesus Pineda-Ramirez, Khamal Anglin, Michelle C. Davidson, Jessica Y. Chen, Maya Fortes-Cobby, Sara Park, Ana Martinez, Matthew So, Aidan Donovan, Badri Viswanathan, Eugene T. Richardson, David R. McIlwain, Brice Gaudilliere, Rachel L. Rutishauser, Ahmed Chenna, Christos Petropoulos, Terri Wrin, Steven G. Deeks, Glen R. Abedi, Sharon Saydah, Jeffrey N. Martin, Melissa Briggs Hagen, Claire M. Midgley, Michael J. Peluso, Raul Andino
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Research Article COVID-19 Immunology Infectious disease

Circulating neutralizing antibodies and SARS-CoV-2 variant replication following postvaccination infections

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Abstract

The effect of preexisting neutralizing antibodies (NAb) on SARS-CoV-2 shedding in postvaccination infection (PVI) is not well understood. We characterized viral shedding longitudinally in nasal specimens in relation to baseline (pre/periinfection) serum NAb titers in 125 participants infected with SARS-CoV-2 variants. Among 68 vaccinated participants, we quantified the effect of baseline NAb titers on maximum viral RNA titers and infectivity duration. Baseline NAbs were higher and targeted a broader range of variants in participants with monovalent ancestral booster vaccinations compared with those with a primary vaccine series. In Delta infections, baseline NAb titers targeting Delta or Wuhan-Hu-1 correlated negatively with maximum viral RNA. Per log10 increase in Delta-targeting baseline NAb IC50, maximum viral load was reduced –2.43 (95% CI: –3.76, –1.11) log10 nucleocapsid copies, and infectious viral shedding was reduced –2.79 (95% CI: –4.99, –0.60) days. Conversely, in Omicron infections (BA.1, BA.2, BA.4, or BA.5), baseline NAb titers against Omicron lineages or Wuhan-Hu-1 did not predict viral outcomes. Our results provide robust estimates of the effect of baseline NAbs on the magnitude and duration of nasal viral replication after PVI (albeit with an unclear effect on transmission) and show how immune escape variants efficiently evade these modulating effects.

Authors

Miguel A. Garcia-Knight, J. Daniel Kelly, Scott Lu, Michel Tassetto, Sarah A. Goldberg, Amethyst Zhang, Jesus Pineda-Ramirez, Khamal Anglin, Michelle C. Davidson, Jessica Y. Chen, Maya Fortes-Cobby, Sara Park, Ana Martinez, Matthew So, Aidan Donovan, Badri Viswanathan, Eugene T. Richardson, David R. McIlwain, Brice Gaudilliere, Rachel L. Rutishauser, Ahmed Chenna, Christos Petropoulos, Terri Wrin, Steven G. Deeks, Glen R. Abedi, Sharon Saydah, Jeffrey N. Martin, Melissa Briggs Hagen, Claire M. Midgley, Michael J. Peluso, Raul Andino

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Figure 2

The magnitude and breadth of baseline NAb titers in participants with PVI.

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The magnitude and breadth of baseline NAb titers in participants with PV...
(A) NAb titers targeting SARS-CoV-2 variants compared with Wuhan-Hu-1 in participants with PVI who received a primary vaccine series or monovalent booster vaccination. n = 22 participants with recruitment specimens taken > 7 PSO were excluded from the analysis. (B) Comparison of baseline NAb titers targeting the infecting variant (except for BA.5 infections for which responses against BA.2 are shown) between participants with PVIs who received a primary vaccine series or monovalent booster vaccination. Box plots represent the IQR (box), median (line), and IQR × 1.5 values (whiskers). Statistical comparisons were made using a 2-sided Wilcoxon rank sum test. Comparisons with P < 0.1 are shown. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0005.

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