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Open Forum Infect Dis . Association of Cytomegalovirus Serostatus With Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responsiveness in Nu

tetano

Editor, Senior Moderator
Open Forum Infect Dis


. 2023 Feb 4;10(2):ofad063.
doi: 10.1093/ofid/ofad063. eCollection 2023 Feb.
Association of Cytomegalovirus Serostatus With Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responsiveness in Nursing Home Residents and Healthcare Workers


Michael L Freeman[SUP] 1 [/SUP], Oladayo A Oyebanji[SUP] 1 [/SUP], Daniela Moisi[SUP] 1 [/SUP], Michael Payne[SUP] 2 [/SUP], Maegan L Sheehan[SUP] 3 [/SUP], Alejandro B Balazs[SUP] 3 [/SUP], Jürgen Bosch[SUP] 4 [/SUP], Christopher L King[SUP] 2 [/SUP], Stefan Gravenstein[SUP] 4 5 6 [/SUP], Michael M Lederman[SUP] 1 [/SUP], David H Canaday[SUP] 1 7 [/SUP]



Affiliations

Abstract

Background: Latent cytomegalovirus (CMV) infection is immunomodulatory and could affect mRNA vaccine responsiveness. We sought to determine the association of CMV serostatus and prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with antibody (Ab) titers after primary and booster BNT162b2 mRNA vaccinations in healthcare workers (HCWs) and nursing home (NH) residents.
Methods: Nursing home residents (N = 143) and HCWs (N = 107) were vaccinated and serological responses monitored by serum neutralization activity against Wuhan and Omicron (BA.1) strain spike proteins, and by bead-multiplex immunoglobulin G immunoassay to Wuhan spike protein and its receptor-binding domain (RBD). Cytomegalovirus serology and levels of inflammatory biomarkers were also measured.
Results: Severe acute respiratory syndrome coronavirus 2-naive CMV seropositive (CMV[SUP]+[/SUP]) HCWs had significantly reduced Wuhan-neutralizing Ab (P = .013), anti-spike (P = .017), and anti-RBD (P = .011) responses 2 weeks after primary vaccination series compared with responses among CMV seronegative (CMV[SUP]-[/SUP]) HCWs, adjusting for age, sex, and race. Among NH residents without prior SARS-CoV-2 infection, Wuhan-neutralizing Ab titers were similar 2 weeks after primary series but were reduced 6 months later (P = .012) between CMV[SUP]+[/SUP] and CMV[SUP]-[/SUP] subjects. Wuhan-neutralizing Ab titers from CMV[SUP]+[/SUP] NH residents who had prior SARS-CoV-2 infection consistently trended lower than titers from SARS-CoV-2 experienced CMV[SUP]-[/SUP] donors. These impaired Ab responses in CMV[SUP]+[/SUP] versus CMV[SUP]-[/SUP] individuals were not observed after booster vaccination or with prior SARS-CoV-2 infection.
Conclusions: Latent CMV infection adversely affects vaccine-induced responsiveness to SARS-CoV-2 spike protein, a neoantigen not previously encountered, in both HCWs and NH residents. Multiple antigenic challenges may be required for optimal mRNA vaccine immunogenicity in CMV[SUP]+[/SUP] adults.

Keywords: COVID-19; SARS-CoV-2; antibodies; cytomegalovirus; vaccination.
 
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