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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Immunological Memory
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1441793

Vaccine induced mucosal and systemic memory NK/ILCs elicit decreased risk of SIV/SHIV acquisition

Provisionally accepted
Mohammad Arif Rahman Mohammad Arif Rahman *Isabela Silva De Castro Isabela Silva De Castro Luca Schifanella Luca Schifanella Massimiliano Bissa Massimiliano Bissa Genoveffa Franchini Genoveffa Franchini *
  • Animal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, United States

The final, formatted version of the article will be published soon.

    SIV and HIV-based envelope V1-deleted (ΔV1) vaccines, delivered systemically by the DNA/ALVAC/gp120 platform, decrease the risk of mucosal SIV or SHIV acquisition better than V1-replete vaccines. Here we investigated the induction of mucosal and systemic memory-like NK cells as well as antigen-reactive ILC response by DNA/ALVAC/gp120-based vaccination and their role against SIV/SHIV infection. ΔV1 HIV vaccination elicited a higher level of mucosal TNF-a + and CD107 + memory-like NK cells than V1-replete vaccination, suggesting immunogen dependence. Mucosal memory-like NK cells, systemic Granzyme B + memory NK cells, and vaccine-induced mucosal envelop antigen-reactive IL-17 + NKp44 + ILCs, IL-17 + ILC3s, and IL-13 + ILC2 subsets were linked to a lower risk of virus acquisition. Additionally, mucosal memorylike NK cells and mucosal env-reactive IFN-g + ILC1s and env-reactive IL-13 + ILC2 subsets correlated with viral load control. We further observed a positive correlation between postvaccination systemic and mucosal memory-like NK cells, suggesting vaccination enhances the presence of these cells in both compartments. Mucosal and systemic memory-like NK cells positively correlated with V2-specific ADCC responses, a reproducible correlate of reduced risk of SIV/HIV infection. In contrast, an increased risk was associated with the level of mucosal PMA/Ionomycin-induced IFN-g + and CD107 + NKG2A -NKp44 -ILCs. Plasma proteomic analyses demonstrated that suppression of mucosal memory-like NK cells was linked to the level of CCL-19, LT-a, TNFSF-12, and IL-15, suppression of systemic env-reactive Granzyme B + memory-like NK cells was associated with the level of OLR1, CCL3, and OSM, and suppression of IL-17 + ILCs immunity was correlated with the level of IL-6 and CXCL-9. In contrast, FLT3 ligand was associated with promotion of protective mucosal env-reactive IL-17 + responses. These findings emphasize the importance of mucosal memory-like NK cell and envelope-reactive ILC responses for protection against mucosal SIV/SHIV acquisition.

    Keywords: memory-like NK cells, Antigen-reactive ILCs, V2-specific ADCC, Innate memory, trained immunity, SIV/SHIV, Vaccine (DNA/ALVAC/gp120), Cytokines

    Received: 31 May 2024; Accepted: 09 Aug 2024.

    Copyright: © 2024 Rahman, Silva De Castro, Schifanella, Bissa and Franchini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Mohammad Arif Rahman, Animal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, United States
    Genoveffa Franchini, Animal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, United States

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