Dynamics of the Humoral Immune Response to the SARS-CoV-2 mRNA Vaccines in People Living With Human Immunodeficiency Virus-1 (HIV-1)
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| Publicado en: | ProQuest Dissertations and Theses (2025) |
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| Acceso en línea: | Citation/Abstract Full Text - PDF |
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| Resumen: | People living with HIV-1 (PWH) are recommended to be fully vaccinated against SARS-CoV-2. However, men with HIV-1 (MWH) respond to the COVID-19 vaccine with lower immunoglobulin binding and neutralization titers against SARS-CoV-2 than men without HIV-1 (MWOH). Although neutralization is an important protective mechanism against SARS-CoV-2, other mechanisms can play a key role in protection. Therefore, antigen-specific complement activation in vaccinated MWH and MWOH, as well as women with HIV (WWH) and women without HIV (WWOH) was assessed. Subsequently, anti-S IgG in circulation in PWH and PWOH was quantified by indirect ELISA, and factors affecting antibody response such as blood chemistry and CD4 count were analyzed. For complement activation, C3 deposition by antibodies specific for SARS-CoV-2 S1 in PWH and PWOH from the Multicenter AIDS Cohort Study (MACS)/Women’s Interagency HIV Study (WIHS) Combined Cohort Study Clinical Research Sites at Pittsburgh and San Francisco was measured using a bead-based flow cytometry assay and capture C3/C3a ELISA. MWH were observed to have lower anti-S1 IgG than MWOH in response to vaccination, however, differences in the levels of anti-S1 IgG between WWH and WWOH were not detected. When matched on anti-S1 IgG titer, MWH had 10-fold greater C3 deposition than MWOH against the Washington (WA) and Omicron strains. However, the level of complement deposition was similar between WWH and WWOH ex vivo. Antibodies from all PWH still induced a strong activation of the classical complement cascade, indicating that non-neutralizing antibodies that bind to Omicron can mediate protection through complement activation. Collectively, these data suggest that complement activation is a mechanism of protection of SARS-CoV-2 vaccination, and that it can have a greater impact on protection against SARS-CoV-2 variants in the absence of neutralizing antibody titers. It also suggests that antibodies with greater complement activation potency in MWH can compensate for lower antibody titers and indicate that men and women may respond differently to vaccination in the context of HIV. These results highlight a critical mechanism of protection in MWH that can inform further booster vaccination schedules and be applied to the creation of novel vaccination strategies for immunocompromised populations. |
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| ISBN: | 9798291504499 |
| Fuente: | ProQuest Dissertations & Theses Global |