OBJECTIVE
To evaluate the durability of SARS-CoV-2-specific humoral and cellular immune responses after booster vaccination in people living with HIV (PLWH) in a prospective longitudinal cohort study.
METHODS
We analyzed 46 PLWH with no prior history of SARS-CoV-2 infection who received a booster dose. Anti-receptor-binding domain (RBD) IgG concentrations, neutralization titers, and T cell responses were measured over time. The associations between CD4+ T cell count and CD4/CD8 ratio with antibody dynamics were assessed, adjusting for age, sex, and vaccine type.
RESULTS
Anti-RBD IgG and neutralization titers declined significantly over time. Participants with CD4+ T cell counts <500 cells/μL exhibited a 3-fold faster decline in anti-RBD IgG compared to those with ≥500 cells/μL. Neutralization capacity declined similarly across both groups, suggesting that CD4+ T cell count primarily influences antibody quantity rather than functional quality. A lower CD4/CD8 ratio was independently associated with reduced baseline IgG concentrations but did not influence the rate of antibody decay. In a subset of 30 participants, a lower CD4/CD8 ratio was also associated with altered follicular helper (Tfh) CD4+ T cell frequencies and faster decline of Spike-specific Tfh over time.
CONCLUSIONS
CD4+ T cell count influences antibody persistence, while the CD4/CD8 ratio affects initial antibody magnitude and Tfh cell frequencies, highlighting complementary roles in shaping vaccine responses in PLWH.
Roser Navarro-Soler, M. J. Heise, T. Dalhuisen et al.· Journal of Acquired Immune D...· 0 citations
Arenaviruses represent a rapidly expanding group of rodent-borne emerging human pathogens with significant pandemic potential. Diseases caused by these viruses, such as the Old-World Arenavirus (OWA) Lassa virus (LASV), which causes Lassa Fever, and the New-World Arenavirus (NWA) Junin virus (JUNV), which causes hemorrhagic fevers, currently lack effective therapeutics or vaccines. Members of the Arenaviridae family possess bi- or tri-segmented genomes encoding three to four viral proteins: glycoprotein (GP), nucleoprotein (NP), RNA polymerase (L) and matrix protein (Z). A robust T-cell immune response is critical for viral clearance and for limiting disease severity during the early stages of the infection.
Using a primary in vitro immunogenicity assay, we identified Conserved T cell Epitope Regions (CTERs) derived from conserved sequences within OWA and NWA, using LASV and JUNV as respective prototypes. These CTER epitopes were strongly recognized by human CD4+ T cells in vitro and were predicted to provide broad population coverage across diverse ethnicities. CTER constructs were designed based on the number of viral proteins included (GP+N+L, N+L, or L) and were assembled using AlphaFold into stable and unstable forms. Plasmids for OWA and NWA were codon-optimized and subsequently packaged into mRNA constructs.
Our ongoing BDF1 mouse studies demonstrate that the CTER-based T-cell vaccine is both safe and immunogenic, as assessed using a combined activation-induced marker (AIM) and intracellular cytokine (ICS) assay. AIM+ T cells isolated from the spleen and lymph nodes show strong cross-reactive potential across the Arenaviridae family.
With further in vitro and in vivo evaluation, this work represents an initial step toward the development of a pan-arenavirus T-cell vaccine.
CEPI, NIH
Vaccines and Immunotherapy (VAC)
Ziyin Wang, Margret Kim, A. Zúñiga et al.· Journal of Immunology· 0 citations
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
The COVID-19 pandemic highlighted the need for vaccines strategies that elicit broad T cell-mediated immunity against emerging viral families. BetaCoronaviruses - including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS) and SARS-CoV-2 — pose significant pandemic risks due to their zoonotic potential and genetic diversity. In previous work, we identified conserved Spike T cell epitope regions (S-CTERs) within the ancestral Wuhan S protein sequence that demonstrated strong cross-reactive potential across diverse BetaCoronaviruses.
Here, we investigated whether bivalent vaccination (Beta + Omicron) preferentially enhances T cell responses targeting CTERs and improves cross-reactivity across Betacoronavirus subgenera. PBMC samples were collected at baseline (day 0) and post-vaccination (day 90) from a cohort of 60 adults receiving either the Pfizer or Moderna bivalent vaccine. Antigen-specific CD4+ and CD8+ T cell responses were assessed using a combined activation-induced marker (AIM) and intracellular cytokine (ICS) assay in a 25-colour-flow cytometry panel.
Overall, bivalent vaccination did not increase the response magnitude to spike or the relative fraction of S-CTER responses within total spike responses. A trend toward increased cytokine polyfunctionality was observed post-vaccination, but no significant differences were observed between pre- and post-vaccination samples across CTER pools derived from multiple BetaCoV isolates.
These findings suggest that spike-based bivalent vaccination alone cannot direct a T-cell focused response to achieve broad immunity across the BetaCoronaviruses family. Incorporation of additional protein sequences will likely be required to shift response toward the CTER approach. Understanding how bivalent vaccinations shape T cell recognition of CTER pools will be critical for advancing universal BetaCoronavirus vaccine design.
NIH
Vaccines and Immunotherapy (VAC)
Ziyin Wang, Nematullah Waseem, Naomi Peisajovich et al.· Journal of Immunology· 0 citations
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