Persistence of restricted CD4 T cell expansions in SIV-infected macaques resistant to SHIV89.6P superinfection

Abstract

Attempts to evaluate the protective effect of live attenuated SIV vaccine strains have yielded variable results depending on the route of immunization, the level of attenuation, the level of divergence between the vaccine candidate and the challenge. The protective mechanisms induced by these vaccines are still not well understood. In an effort to address whether the diversity of the CD4+ T cell repertoire in cynomolgus macaques plays a role in the immunological protection following SIVmacC8 infection, we have performed a longitudinal follow-up of the CD4 repertoire by heteroduplex tracking assay in macaques mock infected or infected with either the attenuated SIVmacC8 or its homologous SIVmacJ5 and challenged with simian-human immunodeficiency virus (SHIV89.6P). Viral load and CD4 absolute counts were determined in these animals and the presence of SHIV89.6P virus in challenged animals was evaluated by PCR and serology. In all macaques that were protected against the challenging virus, we demonstrated a reduced diversity in the CD4+ TRBV repertoire and a few dominant CD4+ T cell clones during early primary infection. In contrast, CD4 TRBV repertoire in unprotected macaques remained highly diverse. Moreover, some of the CD4 T cell clones that were expanded during primary SIV infection re-emerged after challenge suggesting their role in protection against the challenging virus. These results underline the importance of maintaining the CD4 T cell repertoire developed during acute infection and point to the restriction of the CD4 response to the vaccine as a correlate of protection.

Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status

“…In addition, cerebral tissues were harvested from feline immunodeficiency virus-infected cats (12 weeks old) [44] and RAG1 −/− mice (>52 weeks of age) [47], housed under SPF conditions, from which RNA was prepared as described above. Brain tissues from simian (SIV; n = 10) [48] or simian-human immunodeficiency virus-infected (SHIV; n = 3) [49] or FIV-challenged adult cynomolgus macaques (n = 2) [50] were analyzed by initial preparation of RNA followed by RT-PCR amplification of cDNA and sequencing.…”

Repressive Effect of Primary Virus Replication on Superinfection Correlated with Gut-Derived Central Memory CD4+ T Cells in SHIV-Infected Chinese Rhesus Macaques

“…A correlation between susceptibility to superinfection and T cells from peripheral blood, however, was not observed in their study. In contrast, Salha et al observed that the diversity of the CD4 + T-cell repertoire did play a role in SIV-infected macaques resistant to simian-human immunodeficiency virus (SHIV)89.6P superinfection [14]. Furthermore, Pahar et al later demonstrated that primary infection of macaques with SHIV SF162P3 conferred partial to complete protection against subsequent challenge with the highly pathogenic SIVmac251 and suggested that the preservation of intestinal CD4 + memory T cells might be associated with protection from challenge [15].…”

A critical analysis of the cynomolgus macaque, Macaca fascicularis, as a model to test HIV-1/SIV vaccine efficacy

“…SIV mac C8-and SIV mac J5-vaccinated animals showed protection against SHIV-89.6 with lower CD4 + repertoire and dominant CD4 + T cells [97]. Two versions (NM-3 or NM-3n) of the parental SHIV NM-3rN strain were used as vaccines and animals challenged with SHIV NM-3rN live virus showed protection against NM-3rN [98].…”