Understanding “Hybrid Immunity”: Comparison and Predictors of Humoral Immune Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19) Vaccines
Author:
Epsi Nusrat J12ORCID, Richard Stephanie A12, Lindholm David A34, Mende Katrin123, Ganesan Anuradha125, Huprikar Nikhil5, Lalani Tahaniyat126ORCID, Fries Anthony C7, Maves Ryan C8ORCID, Colombo Rhonda E1249, Larson Derek T1011, Smith Alfred6, Chi Sharon W124, Maldonado Carlos J12, Ewers Evan C10, Jones Milissa U13, Berjohn Catherine M411, Libraty Daniel H1211, Edwards Margaret Sanchez12, English Caroline12, Rozman Julia S12, Mody Rupal M14, Colombo Christopher J49, Samuels Emily C15, Nwachukwu Princess15, Tso Marana S15, Scher Ann I16, Byrne Celia16, Rusiecki Jennifer16, Simons Mark P1, Tribble David1, Broder Christopher C15, Agan Brian K12, Burgess Timothy H1, Laing Eric D15, Pollett Simon D12, Cowden J, Darling M, DeLeon S, Lindholm D, Markelz A, Mende K, Merritt S, Merritt T, Turner N, Wellington T, Bazan S, Love P K, Dimascio-Johnson N, Ewers E, Gallagher K, Larson D, Rutt A, Blair P, Chenoweth J, Clark D, Chambers S, Colombo C, Colombo R, Conlon C, Everson K, Faestel P, Ferguson T, Gordon L, Grogan S, Lis S, Mount C, Musfeldt D, Odineal D, Perreault M, Robb-McGrath W, Sainato R, Schofield C, Skinner C, Stein M, Switzer M, Timlin M, Wood S, Banks S, Carpenter R, Kim L, Kronmann K, Lalani T, Lee T, Smith A, Smith R, Tant R, Warkentien T, Berjohn C, Cammarata S, Kirkland N, Libraty D, Maves R, Utz G, Chi S, Flanagan R, Jones M, Lucas C, Madar C, Miyasato K, Uyehara C, Agan B, Andronescu L, Austin A, Broder C, Burgess T, Byrne C, Chung K, Davies J, English C, Epsi N, Fox C, Fritschlanski M, Grother M, Hadley A, Hickey P, Laing E, Lanteri C, Livezey J, Malloy A, Mohammed R, Morales C, Nwachukwu P, Olsen C, Parmelee E, Pollett S, Richard S, Rozman J, Rusiecki J, Samuels E, Nwachukwu P, Tso M, Sanchez M, Scher A, Simons M, Snow A, Telu K, Tribble D, Ulomi L, Chao T, Chapleau R, Christian M, Fries A, Harrington C, Hogan V, Huntsberger S, Lanter K, Macias E, Meyer J, Purves S, Reynolds K, Rodriguez J, Starr C, Iskander J, Kamara I, Barton B, Hostler D, Hostler J, Lago K, Maldonado C, Mehrer J, Hunter T, Mejia J, Montes J, Mody R, Resendez R, Sandoval P, Wayman M, Barahona I, Baya A, Ganesan A, Huprikar N, Johnson B, Peel S,
Affiliation:
1. Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences , Bethesda, Maryland , USA 2. Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc , Bethesda, Maryland , USA 3. Brooke Army Medical Center , Fort Sam Houston, Texas , USA 4. Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland , USA 5. Walter Reed National Military Medical Center , Bethesda, Maryland , USA 6. Naval Medical Center Portsmouth , Portsmouth, Virginia , USA 7. US Air Force School of Aerospace Medicine , Dayton, Ohio , USA 8. Wake Forest School of Medicine , Winston-Salem, North Carolina , USA 9. Madigan Army Medical Center , Joint Base Lewis McChord, Washington , USA 10. Fort Belvoir Community Hospital , Fort Belvoir, Virginia , USA 11. Naval Medical Center San Diego , San Diego, California , USA 12. Womack Army Medical Center , Fort Bragg, North Carolina , USA 13. Tripler Army Medical Center , Honolulu, Hawaii , USA 14. William Beaumont Army Medical Center , El Paso, Texas , USA 15. Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences , Bethesda, Maryland , USA 16. Department of Preventive Medicine & Biostatistics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA
Abstract
Abstract
Background
Comparison of humoral responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/ infection (“hybrid immunity”) may clarify predictors of vaccine immunogenicity.
Methods
We studied 2660 US Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike–immunoglobulin G (IgG) responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or subclinical SARS-CoV-2 reinfection from all groups.
Results
Multivariable regression results indicated that vaccine-after-infection anti-spike–IgG responses were higher than infection-alone (P < .01), regardless of prior infection severity. An increased time between infection and vaccination was associated with greater post-vaccination IgG response (P < .01). Vaccination-alone elicited a greater IgG response but more rapid waning of IgG (P < .01) compared with infection-alone (P < .01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared with JNJ-78436735 vaccine-receipt (P < .01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike–IgG response compared to infection-alone (P < .01).
Conclusions
Vaccine-receipt elicited higher anti-spike–IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared with vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.
Funder
Defense Health Program National Institute of Allergy and Infectious Diseases Infectious Disease Clinical Research Program Department of Defense USUHS Henry M. Jackson Foundation for the Advancement of Military Medicine National Institutes of Health
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
Cited by
37 articles.
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