Antibody response durability following three-dose coronavirus disease 2019 vaccination in people with HIV receiving suppressive antiretroviral therapy

Abstract

Background:Limited data exist regarding longer term antibody responses following three-dose coronavirus disease 2019 (COVID-19) vaccination, and the impact of a first SARS-CoV-2 infection during this time, in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART). We quantified wild-type-specific, Omicron BA.1-specific and Omicron BA.5-specific responses up to 6 months post-third dose in 64 PWH and 117 controls who remained COVID-19-naive or experienced their first SARS-CoV-2 infection during this time.Design:Longitudinal observational cohort.Methods:We quantified wild-type-specific and Omicron-specific anti-Spike receptor-binding domain IgG concentrations, ACE2 displacement activities and live virus neutralization at 1, 3 and 6 months post-third vaccine dose.Results:Third doses boosted all antibody measures above two-dose levels, but BA.1-specific responses remained significantly lower than wild-type-specific ones, with BA.5-specific responses lower still. Serum IgG concentrations declined at similar rates in COVID-19-naive PWH and controls post-third dose (median wild-type-specific and BA.1-specific half-lives were between 66 and 74 days for both groups). Antibody function also declined significantly yet comparably between groups: 6 months post-third dose, BA.1-specific neutralization was undetectable in more than 80% of COVID-19 naive PWH and more than 90% of controls. Breakthrough SARS-CoV-2 infection boosted antibody concentrations and function significantly above vaccine-induced levels in both PWH and controls, though BA.5-specific neutralization remained significantly poorer than BA.1 even post-breakthrough.Conclusion:Following three-dose COVID-19 vaccination, antibody response durability in PWH receiving ART is comparable with controls. PWH also mounted strong responses to breakthrough infection. 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.

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy

“…NtAb titers to BA.5 were significantly lower with respect to titers to B.1 six months after the third dose of the BNT162b2 vaccine in a cohort of HIV-positive subjects, mostly on successful ART. This result is in agreement with previously reported data in patients receiving three vaccine doses and having NtAb tested about one month [5,27] and eight months [28] after the third dose. The subjects enrolled in the first study [27] were HIV-positive patients on ART with a median CD4+ T cell count > 500 cells/mm 3 , while subjects included in the studies by Cheng et al [5] and by Anichini et al [28] were likely HIV-uninfected (no information was reported).…”

“…This result is in agreement with previously reported data in patients receiving three vaccine doses and having NtAb tested about one month [5,27] and eight months [28] after the third dose. The subjects enrolled in the first study [27] were HIV-positive patients on ART with a median CD4+ T cell count > 500 cells/mm 3 , while subjects included in the studies by Cheng et al [5] and by Anichini et al [28] were likely HIV-uninfected (no information was reported). Taken together, all these results suggest that the striking divergence of Omicron BA.5 is the major driver for vaccine escape and that the NtAb response in immune restored HIV-positive subjects is similar to that occurring in HIV-negative patients [27,29].…”

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV

“…At 6 months after the third vaccination, the efficacy of the NAb response against the SARS-CoV-2 strains was inadequate in both cohorts; this was especially true for the Omicron BA.5.2 variant. A similar phenomenon was reported by Lapointe et al and Zhan et al (10,13). Given that none of the PLWH exhibited neutralization activity against Omicron BA.5.2, we analyzed the sera from HCs to see whether the persistent immune dysregulation and chronic inflammatory status of PLWH (32) reduced their ability to mount a protective NAb response against Omicron (30).…”

“…The weak neutralizing ability of NAbs against Omicron BA.5.2 observed in our study could be attributed to a longer interval for blood collection or the difference between COVID-19 vaccines. Another possible explanation is the differences in the immunogenicity of the BA.5.2 and BA.1 Omicron variants (10,13). At 6 months after the third vaccination, the efficacy of the NAb response against the SARS-CoV-2 strains was inadequate in both cohorts; this was especially true for the Omicron BA.5.2 variant.…”

“…Moreover, a South African study by Khan et al showed that inoculating PLWH with a single dose of the Ad26.CoV2.S vaccine induced a considerable NAb response against the Delta variant (8). Very recently, inoculation of PLWH with a third dose of an mRNA COVID-19 vaccine was shown to elicit a robust NAb response against the Omicron BA.1 variant (9,10). The emergence of an increasing number of Omicron sub-lineages, which have a higher propensity for immune evasion compared with the Omicron variant BA.1, has been reported (11,12).…”