Biology subjects

Gallouet, A.-S.

Publications and source records attributed to Gallouet, A.-S..

3 recordsLinked to original sources

bioRxiv2026

Dual blockade of LILRB1 and LILRB2 enhances antiviral immune responses in SIV infection

Restoring effective antiviral immunity remains a major challenge in HIV infection. Among emerging immune checkpoint molecules, the inhibitory receptors LILRB1 and LILRB2 have been proposed as therapeutic targets, yet their in vivo function remains undefined due to the lack of cross-reactive blocking antibodies for relevant preclinical models. To address this, we developed a dual-specific blocking monoclonal antibody, mac20G10, targeting cynomolgus macaque LILRB1 and LILRB2 and assessed its immunomodulatory activity in an SIV model of infection. Pharmacodynamics analyses demonstrated that mac20G10 persisted in circulation and engaged target myeloid cells for up to 14 days without detectable adverse effects. A single administration prior to SIVmac251 infection enhanced early myeloid immune activation, characterized by increased frequencies of CD80+ pDC and CD80+ monocyte/macrophage subsets in blood and lymphoid tissues. These changes were accompanied by increased plasma levels of IFN-{lambda}, IL8, and IL-1RA during acute infection. Although viral replication remained unchanged, mac20G10 treatment promoted the development of SIV-specific memory CD8 T-cell responses. Together, these findings provide in vivo evidence that LILRB1 and LILRB2 function as myeloid immune checkpoints restraining antiviral priming, supporting this pathway as a rational target for combination immunotherapeutic strategies aimed at achieving durable HIV remission during analytic treatment interruption.

immunology↗

bioRxiv2021

The route of vaccine administration determines whether blood neutrophils undergo long-term phenotypic modifications

Innate immunity modulates adaptive immunity and defines the magnitude, quality, and longevity of antigen-specific T- and B- cell immune memory. Various vaccine and administration factors influence the immune response to vaccination, including the route of vaccine delivery. We studied the dynamics of innate cell responses in blood using a preclinical model of non-human primates immunized with a live attenuated vaccinia virus, Modified vaccinia virus Ankara (MVA), and mass cytometry. We previously showed that MVA induces a strong, early, and transient innate response, but also late phenotypic modifications of blood myeloid cells after two months when injected subcutaneously. Here, we show that the early innate effector cell responses and plasma inflammatory cytokine profiles differ between subcutaneous and intradermal vaccine injection. Additionally, we show that the intradermal administration fails to induce more highly activated/mature neutrophils long after immunization, in contrast to subcutaneous administration. Different batches of antibodies, staining protocols and generations of mass cytometers were used to generate the two datasets that were compared. Mass cytometry data were analyzed in parallel using the same analytical pipeline based on three successive clustering steps, including SPADE, and categorical heatmaps were compared using the Manhattan distance to measure the similarity between cell cluster phenotypes. Overall, we show that the vaccine per se is not sufficient for the late phenotypic modifications of innate myeloid cells, which are evocative of innate immune training. Its route of administration is also crucial, likely by influencing the early innate response, and systemic inflammation, and the vaccine biodistribution.

immunology↗

bioRxiv2021

Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects Macaques from infection

The SARS-CoV-2 pandemic causes an ongoing global health crisis, which requires efficient and safe vaccination programs. Here, we present synthetic SARS-CoV2 S glycoprotein-coated liposomes that resemble in size and surface structure virus-like particles. Soluble S glycoprotein trimers were stabilized by formaldehyde cross-linking and coated onto lipid vesicles (S-VLP). Immunization of cynomolgus macaques with S-VLPs induced high antibody titers and TH1 CD4+ biased T cell responses. Although antibody responses were initially dominated by RBD specificity, the third immunization boosted non-RBD antibody titers. Antibodies showed potent neutralization against the vaccine strain and the Alpha variant after two immunizations and robust neutralization of Beta and Gamma strains. Challenge of animals with SARS-CoV-2 protected all vaccinated animals by sterilizing immunity. Thus, the S-VLP approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing.

immunology↗