ABSTRACT
Background: Established SARS-CoV-2 NAb tests are labor-intensive. We prospectively measured NAbs vs Wuhan-1 and Omicron BA.2 using the novel GenScript cPass assay and examined correlations with responses measured by gold-standard plaque reduction neutralisation test (PRNT) (Cotugno, Ruggiero et al. Cell Rep 2021) and with anti-Spike IgG quantified by Roche Elecsys. Given the paucity of data, we selected BNT162b2 vaccine recipients with a history of advanced HIV infection (prior AIDS-defining conditions and/or nadir CD4 <200 cells). Method(s): In Mar 2021-Apr 2022, 55 PWH received 2 vaccine doses median 3 weeks apart [IQR 3-3] and a 3rd dose 27 weeks later [23-31]. Plasma samples (n=147) were stored immediately before dose-1 (T0), median 4 weeks [3-5] after dose-2 (T1) and median 13 weeks [9-19] after dose-3 (T2) for batch testing. Result(s): Participants' characteristics: 74% male, 85% white, all on ART, 82% HIV-RNA <50 cps/ml;median age 55 years, ART duration 7 years, nadir CD4 83 cells [36-211], current CD4 440 cells [270-710], CD4:CD8 ratio 0.6 [0.4-1.0];73% had a history of advanced HIV infection;15% received a COVID-19 diagnosis during the study. At T0, T1 and T2, proportions with quantifiable anti-S IgG (>0.8 U/ml) were 11/49 (22%), 50/54 (93%) and 43/43 (100%), respectively;their median anti-S IgG titres were 30 [15-124], 15949 [596-3389] and 8527 [3146-17190] U/ml. Proportions showing Wuhan-1 neutralisation by cPass were 6/50 (12%), 45/53 (85%) and 40/43 (93%), with median neutralisations of 67% [47-70], 97% [91-98] and 98% [98-98] and corresponding NAb titres of 1332 [792-1436], 5354 [3529-6187] and 6242 [5765-6766] U/ml. At T2, 25/28 (89%) showed BA.2 neutralisation by cPass (median 83% [68-93];NAb titre 7836 [3172-12173] U/ml) (Fig 1A). Two participants lacking NAbs at T2 had a history of advanced HIV infection. cPass data were highly correlated with anti-S IgG titres (rho 0.82;p<0.0001) and with PRNT data for both Wuhan-1 (n=27, Fig 1B) and Omicron BA.2 (n=28, Fig 1C). Conclusion(s): cPAss offers a simple methodology for measuring SARS-CoV-2 NAbs. Despite prior advanced HIV infection, neutralising activity improved with successive vaccinations and most participants showed NAbs against both Wuhan-1 and Omicron BA.2 after 3 vaccine doses. (Figure Presented).
ABSTRACT
Background: The pivotal BNT162b2 trials included only ∼60 vaccine recipients, all with well controlled HIV, and there is a need to gather more information on vaccine safety and immunogenicity in diverse populations. This prospective study evaluated solicited and unsolicited adverse events (AEs) and anti-S and anti-NC serological profiles in a diverse cohort of people with HIV undergoing BNT162b2 vaccination (2 doses 3 weeks apart). Methods: Participants completed structured questionnaires modelled on the BNT162b2 trials (FDA submission, Nov 2020) to report solicited and unsolicited AEs in the 7 days after each vaccine dose, indicating severity and duration. Serum samples collected prior to dose-1 (T0) and 3-6 weeks after dose-2 (T1) underwent qualitative anti-NC and quantitative anti-S testing by Elecsys®. Factors associated with T1 anti-S titres were explored in linear regression models including all available parameters. Results: Overall, 259 adults received dose-1 (26% female, 77% white, 44% MSM, 44% history of advanced disease, 31% ≥1 comorbidity, 10% HIV RNA >50 cps/ml [median 122 cps], 7% prior COVID-19 diagnosis, 15% anti-NC positive;median age 48 years, ART duration 7 years, nadir/current CD4 count 225/708 cells/mm3, CD4:CD8 ratio 0.8);257 received dose-2. Local AEs were more common after dose-1 than dose-2 (70% vs. 62%, p=0.015), whereas systemic AEs increased with dose-2 (50% vs 60%;p=0.006) (Fig 1a-c);22% experienced moderate-severe systemic AEs after dose-2. Unsolicited AEs (mainly nausea and light-headedness) were reported by 7% after dose-1 and 9% after dose-2. Among 206 participants with T1 samples, 205 (99%) had measurable anti-S (>0.8 U/ml). Anti-S levels were significantly lower at CD4 counts <200 cells/mm3 (Fig 1d). In adjusted regression analyses, factors associated with anti-S titres comprised anti-NC positivity (fold-change 7.39;95% CI 3.92-13.91;p<0.01), HIV viraemia (FC 0.24;0.11-0.50;p<0.01), reporting moderate-severe systemic AEs after dose-2 (FC 1.77;1.03-3.04;p=0.04) and either the CD4 count (FC 1.01;1.00-1.01;p=0.04) or CD4:CD8 ratio (FC 1.05;1.00-1.10;p=0.05). Conclusion: In this cohort with HIV, AE patterns after vaccination were similar to those seen in the pivotal BNT162b2 trials and most AEs were mild and short-lived. Whilst prior exposure to SARS-CoV-2 predicted higher anti-S responses, CD4 counts <200 cells/mm3 and low-level viraemia predicted reduced anti-S responses, thus identifying a subset potentially vulnerable to reduced vaccine efficacy.