ASP-7373

Purpose: Influenza vaccination of person living with HIV (PLWH) is a powerful means to tackle severe clinical outcomes. Few data on two doses of influenza vaccine in PLWH are available. Research Design: To evaluate the immunogenicity and safety of two doses of vaccine as compared with single dose in PLWH, we searched Pubmed, Embase, and web of science databases for relevant articles (January 2009 to April 2023). Pooled SMD or RR and 95% CI were calculated. Results: A total of 2436 participants from 14 studies were included. Compared to single dose influenza vaccine regimen, the pooled RR of seroprotection and seroconversion for two doses of vaccines was 1.14 (95%CI: 1.08–1.21) and 1.25 (95%CI: 1.16–1.34), respectively; the SMD of GMT was 0.42 (95%CI: 0.35, 0.49). Regarding safety, the fever risk in PLWH receiving two doses of vaccine was 3.42 fold higher than that of single dose vaccine, and the risk of myalgia had a quarter reduction. No serious vaccine-related adverse events were reported. Conclusions: Collectively, two doses of the vaccine are associated with a better immunogenicity and an acceptable safety in PLWH. Two doses of the adjuvant vaccination might be a superior vaccination regimen.nation regimen.

Subunit or inactivated vaccines comprise the majority of vaccines used against viral and bacterial pathogens. However, compared to their live/attenuated counterparts, these vaccines often demonstrate reduced immunogenicity, requiring multiple boosters and or adjuvants to elicit protective immune responses. For this reason, studies of adjuvants and the mechanism through which they can improve inactivated vaccine responses are critical for the development of vaccines with increased efficacy. Studies have shown that the direct conjugation of adjuvant to antigen promotes vaccine immunogenicity, with the advantage of both the adjuvant and antigen targeting the same cell. Using this strategy of direct linkage, we developed an inactivated influenza A (IAV) vaccine that is directly conjugated with the Toll-like receptor 7/8 agonist resiquimod (R848) through a heterobifunctional crosslinker. Previously, we showed that this vaccine resulted in improved protection and viral clearance in newborn nonhuman primates compared to a non-adjuvanted vaccine. We subsequently discovered that the choice of linker used to conjugate R848 to the virus alters the stimulatory activity of the vaccine, promoting increased maturation and proinflammatory cytokine production from DC differentiated in vitro. With this knowledge, we explored how the choice of crosslinker impacts the stimulatory activity of these vaccines. We found that the linker choice alters signaling through the NF-κB pathway in human monocyte-derived dendritic cells (moDCs). Further, we extended our analyses to in vivo differentiated APC present in human peripheral blood, replicating the linker-dependent differences found in in vitro differentiated cells. Finally, we demonstrated in a mouse model that the choice of linker impacts the amount of IAV-specific IgG antibody produced in response to vaccination. These data enhance our understanding of conjugation approaches for improving vaccine immunogenicity.