Circulating neutralizing antibodies and SARS-CoV-2 variant replication following postvaccination infections
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
- Eugene T Richardson (ORCID: https://orcid.org/0000-0001-8437-0671)
- Raul Andino (ORCID: https://orcid.org/0000-0001-5503-9349)
- Jeffrey N. Martin (ORCID: https://orcid.org/0000-0002-9773-3256)
- Melissa Briggs Hagen (ORCID: https://orcid.org/0000-0001-7359-9665)
- Badri Viswanathan (ORCID: https://orcid.org/0009-0001-4779-5037)
- Ahmed Chenna (ORCID: https://orcid.org/0000-0001-6201-2494)
- Claire M. Midgley (ORCID: https://orcid.org/0000-0001-5196-4713)
- Sarah A. Goldberg (ORCID: https://orcid.org/0000-0002-8642-1468)
- Jessica Y. Chen (ORCID: https://orcid.org/0000-0002-4491-2584)
- Brice Gaudillière (ORCID: https://orcid.org/0000-0002-3475-5706)
- Terri Wrin
- Michelle C. Davidson (ORCID: https://orcid.org/0000-0002-5518-9774)
- Glen R. Abedi
- Miguel Garcia-Knight (ORCID: https://orcid.org/0000-0001-9556-3719)
- Christos J. Petropoulos (ORCID: https://orcid.org/0000-0001-5496-8090)
- Ana María Salinas‐Martínez (ORCID: https://orcid.org/0000-0001-9977-4193)
- Michael J. Peluso (ORCID: https://orcid.org/0000-0003-0585-6230)
- Jesus Pineda-Ramirez
- Rachel L. Rutishauser (ORCID: https://orcid.org/0000-0003-3596-059X)
- Sharon Saydah
- Khamal Anglin (ORCID: https://orcid.org/0000-0002-1801-5345)
- David R. McIlwain (ORCID: https://orcid.org/0000-0002-2537-0273)
- Steven G. Deeks (ORCID: https://orcid.org/0000-0001-6371-747X)
- Amethyst Zhang
- Sara Park (ORCID: https://orcid.org/0000-0001-9584-5003)
- John Daniel Kelly (ORCID: https://orcid.org/0000-0002-7616-0321)
- M. So (ORCID: https://orcid.org/0009-0006-4446-8600)
- Michel Tassetto (ORCID: https://orcid.org/0000-0001-5666-8796)
- Scott Lu
- Maya Fortes-Cobby
- Aidan Donovan
Institutions
- Brigham and Women's Hospital (US)
- Centers for Disease Control and Prevention (US)
- San Francisco General Hospital (US)
- San Francisco VA Medical Center (US)
- Harvard University (US)
- University of California, San Francisco (US)
- National Center for Immunization and Respiratory Diseases (US)
- LabCorp (United States) (US)
- San Francisco Foundation (US)
- University of California San Francisco Medical Center (US)
- Center for Global Health (US)
- Centre for Global Health Research (CA)
- Harvard Global Health Institute (US)
- Universidad Nacional Autónoma de México (MX)
- Stanford University (US)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-03-09
- DOI
- https://doi.org/10.1172/jci.insight.185953
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Centers for Disease Control and Prevention