Informing the need for a SARS-CoV-2 booster based upon the immune response among young, healthy adults to variants circulating during late 2023

COVID-19 remains a global public health challenge due to ongoing emergence of new immune-evasive SARS-CoV-2 variants, heterogeneous immunity, poor education campaigns, and suboptimal surveillance. In this cross-sectional study, we evaluated the adaptive immune responses in US active-duty service members who completed a COVID-19 primary vaccine series to 3 previously dominant variants (Ancestral, Delta, BA.5) and compared them to 3 variants currently circulating (XBB.1.5, EG.5, and BA.2.86). Analyses were performed based upon time (within or beyond 12 months) and type (vaccine or infection) of most recent exposure. Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against current circulating variants compared to previous dominant variants. The reduction in antibody response was more pronounced in those whose most recent exposure, regardless if vaccination or infection, was greater than 12 months from study enrollment. In contrast, the CD4+ T cell response was largely consistent across all tested variants. Our study did not show that the type exposure in the last 12 months was a significant factor in determining the magnitude of immune responses. However, the antibody responses to circulating variants were decreased among participants who received the bivalent booster compared to those with an infection in the past 12 months, potentially due to immunological imprinting of the Ancestral strain. Administration of the new XBB.1.5-based booster is likely to enhance cross-reactive humoral immune responses against current SARS-CoV-2 circulating strains. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by funds from the US Bureau of Medicine and Surgery (BUMED) Restore Core Basic Operational Med Research Sciences to HCN and AGL. The study number is NV.6.R22. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of US Naval Medical Research Command (Silver Spring, MD, USA) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.