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A. Cox

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Open access Jul 2026

CpG-Adjuvanted Heplisav-B Induces Strong Th1-Biased Innate Responses Compared to Alum-Adjuvanted HBV Vaccines in PLWH 2308661

Alum-adjuvanted HBV vaccines such as Engerix-B offer limited protection for people living with HIV (PLWH), achieving only 35—70% seroprotection (as defined by HBsAb titers ≥10 mIU/mL). While Heplisav-B’s CpG 1018 adjuvant improves immunogenicity in PLWH, its mechanisms for overcoming HIV-related immune dysfunction are not yet defined. We performed multiplex cytokine/chemokine profiling assays and high-dimensional flow cytometry, including markers to interrogate cellular metabolism, to characterize early innate responses 24 hours after the first dose of Engerix-B or Heplisav-B in PLWH who were non-responders to prior HBV vaccination. Heplisav-B induced robust early innate activation, characterized by significantly elevated IP-10, MCP-2, and IFN-γ versus baseline, consistent with Th1-skewed inflammatory profile that was not observed following Engerix-B vaccination. Heplisav-B produced an increased frequency of B cells following vaccination, but the cellular immunometabolic expression profiles were otherwise not significantly different between the two vaccines 24 hours after vaccination. This suggests that global immune cell proportions were largely maintained despite differences in cytokine induction. However, 24-hour cytokine levels predictive of seroprotection were distinct between vaccines, with low IL-17A production following Heplisav-B and low IL-2 and IL-4 production following Engerix-B being the strongest predictors of antibody responses. Heplisav-B induces stronger Th1-skewed innate responses and increased B cell frequency than Engerix-B in PLWH within the first 24 hours of vaccination, while overall cellular composition and activation remain largely preserved. These findings provide mechanistic insight into how TLR9-targeting adjuvants can enhance vaccine immunogenicity in immunocompromised populations and suggest that response to the two vaccines may be driven through different innate immune pathways. NIH/NIAID R01AI186730 Vaccines and Immunotherapy (VAC)

Jenny M. Lee, Prasanthy Balasubramanian, Yufeng Liu et al. · Journal of Immunology · 0 citations

Open access Jul 2026

Conserved CD4 T-cell responses correlate with antibody neutralization in solid organ transplant recipients after bivalent SARS-CoV-2 vaccination

Introduction Vaccines against SARS-CoV-2 and influenza require reformulation due to viral evolution. It remains unclear how vaccination against evolving antigens influences T-cell responses and the impact of reformulation on T-cell responses to new variants in immunocompromised hosts. Solid organ transplant recipients (SOTRs) had significantly lower antibody levels following vaccination and required repeated boosting during the COVID-19 pandemic. Methods With the introduction of the Omicron spike (S) to the bivalent mRNA vaccines in 2022, the relative contribution of T-cell responses cross-reactive for Omicron mutated S sequences was assessed via intracellular cytokine staining using peptide pools containing conserved or mutated S sequences. Results S-specific CD4 T cells recognize both conserved and Omicron mutated S sequences pre- and post-bivalent vaccination, even in the absence of evidence of prior infection as detected by T-cell responses to a novel peptide pool. CD4 T-cell responses to both conserved and Omicron mutated sequences correlated with antibody pseudo-neutralization of BA.5 S. Importantly, pre-bivalent conserved S CD4 T-cell responses significantly correlated with antibody pseudo-neutralization of BA.5 S post-bivalent. Discussion These results emphasize the importance of conserved and cross-reactive responses in vaccine immunogenicity, providing a mechanism through which repeated boosting enhances vaccine immunogenicity in SOTRs and other immunocompromised populations.

Georgia Stavrakis, Katerina Roznik, Laila Stoddart et al. · Frontiers in Immunology · 0 citations