Abstract
OBJECTIVES: To ensure adequate preparedness of immunocompromised populations for future pandemic waves, it is crucial to assess the humoral immune response of people living with HIV (PLWH) to existing vaccination strategies and major Omicron sublineages following BA.5/BF.7 breakthrough infection (BTI). METHODS: This study enrolled 232 PLWH who had received either the CoronaVac/BBIBP-CorV or ZF2001 vaccine and experienced the BA.5/BF.7 wave in China between January and April 2023. Serum samples from each individual were collected approximately 1-6 months after the last exposure. Immunoglobulin G (IgG) and total antibodies against SARS-CoV-2 were measured using a chemiluminescent immunoassay. Neutralizing antibodies (NAbs) against D614G, BA.5, and XBB.1.5 were detected using a pseudovirus-based neutralization assay. Meanwhile, an Enterprise WeChat link was created to allow PLWH to self-report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and clinical symptoms associated with coronavirus disease 2019 (COVID-19). RESULTS: The Omicron BA.5/BF.7 BTI rate among PLWH was 76.7%. The most commonly reported symptoms were fever, fatigue, and muscle ache. PLWH who experienced BA.5/BF.7 BTI after three doses of inactivated vaccines showed elevated levels of total antibodies, IgG, and NAb titers against D614G and BA.5. In contrast, those who experienced BTI after three doses of ZF2001 vaccines showed the highest NAb titers against D614G and BA.5. However, the neutralizing capacity of antibodies against XBB.1.5 was significantly reduced in both study cohorts. PLWH who had CD4 lymphocyte counts greater than 500 cells/μL demonstrated higher NAb titers against all tested variants and reported a lower incidence of symptoms. CONCLUSION: Hybrid immunity resulting from vaccination and BA.5/BF.7 BTI enhances humoral immune responses in PLWH, which may contribute to improved protection against COVID-19. However, this hybrid immunity offers limited protection against Omicron variant XBB.1.5. Regular monitoring of immune responses to new vaccines targeting emerging variants is crucial for optimizing COVID-19 prevention strategies in PLWH.