Mosaic HIV-1 vaccine and SHIV challenge strain V2 loop sequence identity and protection in primates

Kanika Vanshylla; Jeroen Tolboom; Kathryn E Stephenson; Karin Feddes-de Boer; Annemiek Verwilligen; Sietske Karla Rosendahl Huber; Lucy Rutten; Hanneke Schuitemaker; Roland C Zahn; Dan H Barouch; Frank Wegmann

doi:10.1038/s41541-024-00974-1

Mosaic HIV-1 vaccine and SHIV challenge strain V2 loop sequence identity and protection in primates

NPJ Vaccines. 2024 Sep 30;9(1):179. doi: 10.1038/s41541-024-00974-1.

Authors

Affiliations

¹ Janssen Vaccines & Prevention, Leiden, The Netherlands.
² Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
³ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
⁴ Harvard Medical School, Boston, MA, USA.
⁵ Janssen Vaccines & Prevention, Leiden, The Netherlands. frank.wegmann.1@gmail.com.

Abstract

The failure of human vaccine efficacy trials assessing a mosaic HIV-1 vaccine calls into question the translatability of preclinical SHIV challenge studies that demonstrated high efficacy of this vaccine in primates. Here we present a post hoc immune correlates analysis of HIV-1 Env peptide-binding antibody responses from the NHP13-19 study identifying the V2 loop as the principal correlate of protection in primates. Moreover, we found high V2 loop sequence identity between the Mos1 vaccine component and the SHIV challenge strain, while the vaccine showed considerably lower V2 identity to globally circulating HIV-1 sequences. Thus, the induction of immune responses against the V2 epitope, which had exceptional identity between the vaccine and challenge Env strains, may have contributed to the high protection in primates.