The concept of intravascular immunity is reshaping our understanding of immune surveillance, challenging the traditional view that immune responses are confined to either tissue parenchyma or the bloodstream. Our pilot study utilized intravascular staining (ivs) in rhesus macaques (RhM) to spatially distinguish pulmonary vasculature-associated (ivs+) CD8+ T cells from interstitial (ivs-) T cells. Single-cell RNA sequencing and flow cytometry revealed that ivs+ T cells are not passive blood contaminants but rather a distinct, "resident-like" population enriched in cytotoxic effectors, with elevated expression of transcripts associated with tissue residency, cell adhesion, and vascular/platelet interactions, while ivs- T cells exhibited a classic TRM signature. The presence of SIV-specific tetramer+ ivs+ CD8+ T cells in infected RhM suggests a role in antiviral defense within the lung vasculature. These findings provide new insight into intravascular immunity, highlighting a unique population of CD8+ T cells as potential pulmonary vascular sentinels poised for rapid immune responses.
© 2025 The Author(s).

Nonhuman primates have a key role in the evaluation of novel therapeutics including vaccine and drug development. Monitoring biochemical and hematological parameters of macaques is critical to understand toxicity and safety, but general reference intervals following standardized guidelines remain to be determined. Here we compiled multiple internal datasets to define normal ranges of classical biochemical and hematological parameters in Indian and Chinese rhesus macaques as well as cynomolgus macaques. Furthermore, the combination of hematological data with phenotypic information of cells obtained by flow cytometry enabled analyses of specific immune cell subsets. We found that vaccination generally induced transient changes at 24 h in cell frequencies accompanied by fluctuation in selected liver enzymes and metabolites. However, most parameters remained within our identified reference intervals. These deviations did not lead to noticeable side effects. Fluctuation in selected biochemical and hematological parameters was accompanied with differentiation of CD14+CD16+ intermediate monocytes and upregulation of genes associated with interleukin-1 signaling. By contrast, two animals with noticeable side effects showed sustained deviations. This study provides insights into baseline and vaccine-induced biochemical and hematological profiles of healthy macaques, facilitating the interpretation of toxicity and safety assessments in preclinical trials of novel therapies.
© 2025. The Author(s).

In autoimmunity, an imbalance of effector (Teff) and regulatory (Treg)T cells contributes to inflammation and tissue destruction. CD2, highly expressed on Teff and at lower levels on Treg and naive T cells (Tn), is an attractive target for depleting Teff at sites of inflammation. SBT115301 is a second generation CD2-targeting fusion protein containing the cognate receptor of CD2, lymphocyte function associated antigen-3 (LFA-3; CD58). In in vitro and in vivo studies, SBT115301 preferentially decreased CD2hi-expressing Teff cells compared to Treg and Tn. In a phase 1 clinical trial, SBT115301 selectively reduced memory T cells. SBT115301 was well tolerated aside from decreases of CD4+ T cells in some participants in the highest dose IM and IV cohorts. Anti-drug antibodies decreased exposure of SBT115301 in some participants without affecting the pharmacodynamics. These data support further study of SBT115301 as a monotherapy or in combination with other drugs in autoimmune indications.
© 2025 Sonoma Biotherapeutics.

A SARS-CoV-2 spike DNA vaccine formulated with a cationic nanoparticle emulsion (LION) was tested in Rhesus macaques. It induced robust, long-lasting (>2 years) cellular and humoral immunity, including increased neutralization breadth. T cell responses were predominantly CD8+, in contrast to other DNA vaccines. A rapid transient cytokine/chemokine response was associated with expansion and trafficking of myeloid cells and lymphocytes. Increased proliferation and dynamic changes between blood and lymph node (LN) were found for monocyte-derived cells, dendritic cells, and B and T cells, resulting in activation of LN and expansion of germinal centers (GCs), likely critical in shaping long-lasting adaptive immunity. Significant GC expansion of B, CD4-, and CD8- cells, including the Tfc3 subset, reflects a balanced immune response, including antibody (Ab) development. DNA/LION vaccination activates myeloid and lymphoid cells in blood and LN and promotes effective antigen presentation, resulting in sustained antigen-specific cellular and humoral responses, emerging as an effective DNA vaccine delivery platform.

Rare naive B cells have special pathogen-recognition features that enable outsized contributions to protective immunity but infrequently participate in immune responses. We investigatee how germline-targeting vaccine delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (<1-in-50 million) in non-human primates. Only escalating dose (ED) priming immunization using the saponin adjuvant SMNP elicited detectable BG18-like cells in germinal centers (GCs) compared with other conditions. All groups had strong GC responses, but only ED+SMNP and bolus+SMNP induced BG18-like memory B cells in >50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP but scarce BG18-like B cells. Following homologous boosting, BG18-like memory B cells were present in a bolus priming group but with lower somatic hypermutation and affinities than ED+SMNP. This outcome inversely associated with post-prime antibody titers, suggesting antibody feedback significantly influences rare precursor B cell responses. Thus, antigen and inflammatory stimuli extensively impact priming and affinity maturation of rare B cells.
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.