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31st International Dynamics & Evolution of Human Viruses

Jun 19 – 22, 2024
Squamish, BC, Canada
Canada/Pacific timezone
This conference is now SOLD OUT for in-person registration. Virtual registration is still available.

Maureen Helinski

SARS-COV-2 VARIANT REPLACEMENT CONSTRAINS VACCINE-SPECIFIC VIRAL DIVERSIFICATION

Not scheduled
20m
Squamish, BC, Canada

Squamish, BC, Canada
Oral Vaccines & immune escape

Speaker

Bethany L Dearlove (U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA)

Description

COVID-19 vaccine breakthrough infections have been important for all circulating SARS-CoV-2 variant periods, but the contribution of vaccine specific SARS-CoV-2 viral diversification to vaccine failure remains unclear.

This study analyzed US Military Health System beneficiaries with SARS-CoV-2 infection and who enrolled in ten Military Treatment Facilities between December 2020 and April 2022 as part of the EPICC study. PCR positive upper respiratory swabs underwent sequencing using the Illumina NextSeq 550 platform. We curated 565 SARS-CoV-2 full spike sequences annotated with vaccination status and subject reported data. We accounted for spatial sampling bias with geographic stratification and background public spike sequences from GISAID. We compared (i) the distance of infection spike sequences from the vaccine spike sequence, Wuhan-Hu-1, (ii) site-specific spike sequence amino acid differences and (iii) timing of the emergence of Alpha, Delta, and Omicron variants, between the unvaccinated and vaccine breakthrough infection groups.

We found limited evidence indicating that vaccination was associated with increased substitutions in the SARS-CoV-2 spike, and we show little to no evidence of a substantial sieve effect within major variants; rather we show that rapid variant replacement constrained intra-genotype COVID-19 vaccine strain immune escape. There was no statistically significant difference in the timing of Alpha, Delta and Omicron infection in the vaccinated and unvaccinated groups.

These data suggest that, during periods of rapid SARS-CoV-2 variant replacement, vaccine-mediated effects are subsumed with other drivers of viral diversity. We illustrate a comprehensive bioinformatic approach to assess for strain-specific genetic signatures of vaccine failure outside the context of a vaccine efficacy trial. These methods may be useful in the development and evaluation of future vaccines for COVID-19 and other respiratory viral illnesses.

Disclaimers: The views expressed are those of the authors and do not reflect the official policy of the USUHS, Department of the Army, Department of the Navy, the Department of the Air Force, the Department of Defense, the Defense Health Agency, or the U.S. Government and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF).

Potential conflicts of interest. S. D. P., T. H. B, D.R.T, and M.P.S. report that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and the Henry M. Jackson Foundation (HJF) were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both of these trials were part of the US Government COVID-19 response. Neither is related to the work presented here.

Funding: This work was supported by awards from the Defense Health Program (HU00012020067) and the National Institute of Allergy and Infectious Disease (HU00011920111). The protocol was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USUHS) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded in part by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, under an interagency agreement (Y1-AI-5072). Work by the Military HIV Research Program was supported by a cooperative agreement (WW81XWH-18-2-0040) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD).

Primary authors

Bethany L Dearlove (U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA) Anthony C Fries (US Air Force School of Aerospace Medicine, Wright-Patterson, Ohio, USA) Nusrat J Epsi (Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) Stephanie A Richard (Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) Anuradha Ganesan (Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Walter Reed National Military Medical Center, Bethesda, Maryland, USA) Nikhil Huprikar (Walter Reed National Military Medical Center, Bethesda, Maryland, USA) David A Lindholm (Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Brooke Army Medical Center, Joint Base San Antonio–Fort Sam Houston, Texas, USA) Katrin Mende (Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Brooke Army Medical Center, Joint Base San Antonio–Fort Sam Houston, Texas, USA) Rhonda E Colombo (Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Madigan Army Medical Center, Joint Base Lewis McChord, Washington, USA) Christopher Colombo (Madigan Army Medical Center, Joint Base Lewis McChord, Washington, USA) Derek T Larson (Alexander T. Augusta Military Medical Center, Virginia, USA) Evan C Ewers (Alexander T. Augusta Military Medical Center, Virginia, USA) Tahaniyat Lalani (Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Naval Medical Center Portsmouth, Portsmouth, Virginia, USA) Alfred G Smith (Naval Medical Center Portsmouth, Portsmouth, Virginia, USA) Catherine M Berjohn (Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; Naval Medical Center San Diego, San Diego, California, USA) Ryan C Maves (Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA) Milissa U Jones (Department of Pediatrics, Uniformed Services University, Bethesda, Maryland USA) David Saunders (Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) Carlos J Maldonado (Womack Army Medical Center, Fort Liberty, North Carolina, USA) Rupal M Mody (William Beaumont Army Medical Center, El Paso, Texas, USA) Samantha E Bazan (Carl R. Darnall Army Medical Center, Fort Cavazos, Texas, USA) David R Tribble (Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) Timothy Burgess (Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) Mark P Simons (Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) Brian K Agan (Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) Simon D Pollett (Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) Morgane Rolland (U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA)

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