@article{680a30e918b44e1a9c1d69e4cc5fb273,
title = "Association of Frailty, Age, and Biological Sex with Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine–Induced Immunity in Older Adults",
abstract = "Background. Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. Methods. Plasma samples were collected from older adults (aged 75–98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18–74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). Results. Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. Conclusions. Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.",
keywords = "ACE2, Delta, Omicron, aging, antibody response, frailty, sex differences",
author = "Shapiro, {Janna R.} and Ioannis Sitaras and Park, {Han Sol} and Aytenfisu, {Tihitina Y.} and Christopher Caputo and Maggie Li and John Lee and Johnston, {Trevor S.} and Huifen Li and Camille Wouters and Pricila Hauk and Henning Jacobsen and Yukang Li and Engle Abrams and Steve Yoon and Kocot, {Andrew J.} and Tianrui Yang and Yushu Huang and Cramer, {Steven M.} and Betenbaugh, {Michael J.} and Debes, {Amanda K.} and Rosemary Morgan and Milstone, {Aaron M.} and Karaba, {Andrew H.} and Andrew Pekosz and Leng, {Sean X.} and Klein, {Sabra L.}",
note = "Funding Information: Potential conflicts of interest. I. S., M. L., C. W., S. Y., and A. P. received funding for their institution from NIAID/NIH (grants N272201400007C and 75N93021C00045) and from the CDC (grant 75D30121C11061). A. J. K., S. M. C., and M. J. B. received grant support from the National Institute for Innovation in Manufacturing Biopharmaceuticals consortium, which that went to their institution. R. M. was supported by the Office of Research on women's Health and the NIA, NIH (grant U54AG062333). A. M. M. has received grants or contracts from the Agency for Healthcare Research and Quality, the CDC, the NIH, and Merck. A. H. K. received NIAID funding (grant K08AI156021) and consulting fees from Roche. S. X. L. received NIH grants for their institution (grants U54AG062333, R01AI108907, R21AG059742, UH2AG056933, U01AI35042, R01AG060825, and U01AI165826); funding for their institution from Cybersecurity and Infrastructure Security Agency, MMAAP, the Sanofi Pasteur grant project and the Howard and Abby Milstein Foundation; and honoraria for participating in the Sanofi Pasteur COVID-19 Vaccine International Advisory Board, the Sanofi Pasteur Speakers Bureau for Influenza Vaccines, and the GSK Speakers Bureau for Herpes Zoster Vaccine Shingrix. They are also the president of the MMAAP foundation. S. L. K. received support from the NIA/NIH (grant U54AG062333) and NIH/National Cancer Institute/NIH (grant U54CA260492) and is a board member for the NIH{\textquoteright}s Advisory Committee on Research on women's Health and an editor for PloS Pathogens and the Journal of Virology. All other authors report no potential conflicts. Publisher Copyright: {\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.",
year = "2022",
month = aug,
day = "15",
doi = "10.1093/cid/ciac397",
language = "English (US)",
volume = "75",
pages = "S61--S71",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "1",
}