Background Varicella-zoster virus (VZV), also known as chickenpox virus, constitutes a promising vector for a successful HIV vaccine. As an effort to scrutinize its potential, we are characterizing the susceptibility of VZV-specific CD4 T cells to HIV infection and the phenotypic profile of both CD4 and CD8 T cells.

Methods Blood T cells isolated from a cohort of healthy Kenyan women with pre-immunity to VZV (NCT02514018) were stimulated in vitro using 15-mer peptides representing VZV glycoprotein E (gE) and VZV Open Reading Frame 4 (ORF4). CD4 and CD8 T cell memory phenotypes were characterized by flow cytometry based on the expression of CCR7/CD45RA. The activation status of VZV-specific CD4 T cells was measured by the expression of HLA-DR, CD69, and CD25 after 6-day stimulation with gE and ORF4 peptides. Susceptibility to HIV infection was assessed using in vitro infection with a CCR5-tropic virus. DMSO and CMV peptides were used as negative and positive controls, respectively.

Results A similar frequency of central memory CD4 T cells (T_CM) (median 24%, IQR 18%-32%) and effector memory CD4 T cells (T_EM) (median 27%, IQR 20%-32%) was observed in our cohort. The predominant CD8 memory subtype was T_EMRA (median 28%, IQR 21%-40%) followed by T_EM cells (median 12%, IQR 8%-19%) (n=45). Preliminary results show our ability to expand VZV-specific cells in culture using gE and ORF4 as stimuli and that these cells highly express the marker HLA-DR. Their susceptibility to in vitro HIV infection is currently under investigation using CMV-specific cells as comparator.

Conclusion A viral vector able to sustain CD8 T_EM responses without fueling the immune system with HIV target cells constitutes an ideal candidate for an HIV vaccine. Hence, our study sheds light on key aspects of VZV-specific immunity that will help determining its future as a vector in an HIV vaccine.

Disclosure No significant relationships.