Mucosal antibody responses to vaccines targeting SIV protease cleavage sites or full-length Gag and Env proteins in Mauritian cynomolgus macaques.

Hongzhao Li,So-Yon Lim,Tamara G Dacoba,Lewis R Liu,James B Whitney,Dane Schalk,Yanmin Wan,Binhua Liang,Lin Li,Yan Hai,Nancy Schultz-Darken,Francis A Plummer,Ma Luo,Nikki Toledo,Mohammad Abul Kashem,José Crecente‐Campo ,Eva G Rakasz ,Robert W Omange ,María José Alonso

doi:10.1371/journal.pone.0202997

Abstract

HIV mutates rapidly and infects CD4+ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4+ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV immunogens at the female genital tract. Bio-Plex and Western blot analyses of cervicovaginal lavage samples showed that both the PCS and Gag/Env vaccines can elicit mucosal IgG antibody responses to SIV immunogens. Significantly higher increase of anti-PCS antibodies was induced by the PCS vaccine than by the Gag/Env vaccine (p<0.0001). The effect of the mucosal antibody responses in protection from repeated low dose pathogenic SIVmac251 challenges is being evaluated.

Highlights

Development of an effective vaccine to human immunodeficiency virus type 1 (HIV) has proven to be a daunting task
In this study we examined mucosal antibodies induced by two different modalities of candidate HIV/Simian immunodeficiency virus (SIV) vaccines, a vaccine targeting short peptide sequences overlapping the 12 protease cleavage sites and a vaccine targeting full Gag and Env of SIVmac239
Since 90% of HIV transmissions occur through the mucosal route [68] and male to female sexual transmissions account for more than half of all HIV infections [53], it is important to test whether a candidate vaccine can induce mucosal immune responses to HIV/SIV antigens

Summary

Introduction

Development of an effective vaccine to human immunodeficiency virus type 1 (HIV) has proven to be a daunting task. Even subtle disturbance can be sufficient to interrupt this delicately balanced process and drive it toward a non-productive end [20, 23, 24, 26] Consistent with their critical function, the sequences surrounding the PCSs are highly conserved among major HIV subtypes [27]. A HIV vaccine targeting the viral protease cleavage sites (PCSs) has been proposed for its ability to generate antiviral immune responses, disrupt HIV maturation and limit target cell activation [10, 18, 27]

Methods

Results

Conclusion