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

Abstract

IntroductionVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals.MethodsA total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis.ResultsAt 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron.DiscussionThis study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges.Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.

Antibody neutralization capacity after COVID-19 vaccination in people with HIV (CIHR Canadian HIV trials network 328)

“…However, other groups have reported diminished anti-S vaccine response and neutralization capacity in PWH vs. HIV-uninfected controls [ 27 , 28 ]. Differences amongst findings in PWH may be because of discrepancies in multimorbidity burden in older adults, type and number of vaccines received and time interval between vaccinations [ 27 – 30 ]. Third dose vaccines elicited better neutralizing antibody responses in PWH with longer time intervals between vaccines [ 30 ].…”

“…Differences amongst findings in PWH may be because of discrepancies in multimorbidity burden in older adults, type and number of vaccines received and time interval between vaccinations [ 27 – 30 ]. Third dose vaccines elicited better neutralizing antibody responses in PWH with longer time intervals between vaccines [ 30 ]. Furthermore, although there is evidence for sex-based differences in humoral immune response with certain types of vaccinations in HIV-negative populations [ 30 ], we and others have not observed any sex difference in antibody level or neutralization capacity in the context of COVID-19 vaccination [ 10 – 12 , 19 ].…”

“…Third dose vaccines elicited better neutralizing antibody responses in PWH with longer time intervals between vaccines [ 30 ]. Furthermore, although there is evidence for sex-based differences in humoral immune response with certain types of vaccinations in HIV-negative populations [ 30 ], we and others have not observed any sex difference in antibody level or neutralization capacity in the context of COVID-19 vaccination [ 10 – 12 , 19 ]. Moreover, in both PWH vs. HIV-negative controls, some participants had a high antibody titre but low ID50.…”

Immunogenicity and effectiveness of COVID-19 booster vaccination among people living with HIV: a systematic review and meta-analysis

“…A total of seven eligible studies ( 43 , 47 , 51 , 53 , 54 , 59 , 61 ) involved PLWH with T-cell counts < 200, none of which had HC. The results showed a pooled IRR of 86.27% (95% CI, 65.35–99.07).…”

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

“…Anti-SARS-CoV-2 vaccines are safe, and they were shown to reduce morbidity and mortality: real-word data confirmed the data reported in registration studies [12][13][14]. The third dose and its timing have a peculiar role: HIV-positive patients who received 2 vaccine doses are at higher risk of breakthrough infections with respect to HIV-negative subjects, but the third BNT162b2 dose has a protective role [15], and a higher neutralizing antibody seronversion rate was described in HIV-positive patients receiving the third dose of the inactivated COVID-19 vaccine after 5 months with respect to the 3-month interval, especially in subjects with a CD4 count <200 cells/mm 3 [16].…”