PWH also mounted strong reactions to breakthrough illness. controls. Breakthrough SARS-CoV-2 illness boosted antibody concentrations and function significantly above vaccine-induced levels in both PWH and settings, though BA.5-specific neutralization remained significantly poorer than BA. 1 even post-breakthrough. == Summary: == Following three-dose COVID-19 vaccination, antibody response durability in PWH receiving ART is comparable with controls. PWH also mounted strong reactions to breakthrough illness. Due to temporal response declines, however, COVID-19-naive individuals, regardless of HIV status, would benefit from a fourth dose within 6 months of their third. Keywords:antibody, coronavirus disease 2019, HIV, humoral immunity, cross immunity, Omicron BA.1, Omicron BA.5, third dose, vaccines, viral neutralization == Introduction == In British Columbia (BC), Canada, third doses of coronavirus disease 2019 (COVID-19) monovalent mRNA vaccines were introduced in November 2021, initially to individuals at risk of severe COVID-19 outcomes, including some people with HIV (PWH). Whether offered as part of a primary vaccine series or a booster, third doses help to maintain systemic immunity and enhance safety against illness by viral variants [14]. Despite being effective at preventing severe disease because of SARS-CoV-2, third doses provide limited safety against transmission of Omicron subvariants, including BA.1 and BA.5 [510], which were estimated to have infected more than 60% of Canadians by August 2022, despite approximately 50% uptake of third vaccine doses [1113]. Longitudinal monitoring of immune responses post-third dose in PWH is critical to inform the timing of future immunizations with this group. Though some data are available on DPH initial immunogenicity to third COVID-19 vaccine doses in PWH [1416], no studies to our knowledge have assessed the longer term toughness of post-third dose responses with this human population. Furthermore, despite the high incidence of first-time SARS-CoV-2 infections after three vaccine doses, no studies to our knowledge possess examined the effect of such infections on reactions in PWH. Here, we lengthen prior observations from our cohort [14,17] by quantifying wild-type-specific, Omicron BA.1-specific and BA.5-specific responses up to 6 months post-third vaccine dose in 64 PWH and 117 controls who either remained COVID-19-naive or experienced their 1st (presumably Omicron [18]) SARS-CoV-2 infection, during this period. == Methods == == Participants == Our cohort was explained previously [14]. The present study included 64 PWH and 117 settings who remained COVID-19-naive until at least one month post-third vaccine dose. Breakthrough SARS-CoV-2 infections were recognized through self-reported PCR and/or rapid-antigen test results and the presence of serum antibodies against Nucleocapsid (N) using the Elecsys Anti-SARS-CoV-2 assay (Roche Diagnostics, Laval, Quebec, Canada). == Ethics authorization == This study was authorized by the University or college of English Columbia/Providence Healthcare and Simon Fraser University or college Research Ethics Boards. All participants offered written educated consent. == Antibody assays == Assays were performed as previously explained [14,19]. IgG-binding antibodies in serum were measured against the SARS-CoV-2 Spike Receptor Binding Website (RBD) using the V-plex SARS-CoV-2 (IgG) ELISA kit (Panel 22; Meso Level Diagnostics, Rockville, Maryland, USA), which features wild-type and Omicron-BA.1 RBD antigens, on a Meso QuickPlex SQ120 instrument. Serum was diluted 1 : 10000 and reported in WHO International Standard Binding Antibody Devices (BAU)/ml using the manufacturer-supplied conversions. Surrogate disease neutralization activity [20] in serum was measured by competition ELISA using the same kit [Panel 22; V-plex SARS-CoV-2 (ACE2)] to measure blockade of the RBD-ACE2 receptor connection. Sera were diluted 1 DPH : 40 and results reported as % ACE2 displacement. Disease neutralizing activity in plasma was assessed using live wild-type (USA-WA1/2020; BEI Resources, Manassas, Virginia, USA), and two local isolates identified as Omicron BA.1 (GISAID Accession# EPI_ISL_9805779) and Omicron BA.5 (GISAID Accession# EPI_ISL_15226696) on VeroE6-TMPRSS2 (JCRB-1819) target cells [19]. Disease stocks were diluted to DPH 50 TCID50/200 l in the presence of serial two-fold plasma dilutions (1/20 to 1/2560) and added to target cells in triplicate. Viral cytopathic effects (CPE) were recorded 3 days post-infection. Neutralization was reported as the highest reciprocal Epha1 dilution able to prevent.
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