[Show abstract][Hide abstract] ABSTRACT: Previously, replicating adenovirus type 5 host range (Ad5hr)-HIV/SIV recombinant priming in combination with SIV envelope boosting, resulted in significant, durable protection in 39% of rhesus macaques after SIVmac251 challenge. Both Env-specific antibody mediating ADCC, and cellular immunity correlated with protection. Here we evaluate the relative immunogenicities of novel HIV proteins and their contribution to protection in a SHIV89.6P model. All groups were primed with Ad-HIVenv89.6P, SIVgag239, and SIVnef239 recombinants. One group was not boosted, one received HIV89.6Pgp140DeltaCFI protein, and one a novel HIV-1 poly-peptide "peptomer". The HIV89.6Pgp140DeltaCFI protein in adjuvant strongly boosted Env-specific antibody and memory T cell responses in blood and tissue, resulting in significant reductions in acute and set point viremia. Macaques not boosted, showed a significant reduction in set point viremia, a full 32 weeks after the last Ad priming immunization. The HIV peptomer-boosted group showed a trend toward chronic viremia reduction, but was not protected.
[Show abstract][Hide abstract] ABSTRACT: Human herpesvirus-6 (HHV-6) and -7 (HHV-7) are Roseoloviruses within the Betaherpesvirus family, which have a high prevalence and suspected involvement in a number of diseases. Using CODEHOP-based PCR, we identified homologs of both viruses in saliva of pig-tailed macaques, provisionally named MneHV-6 and MneHV-7. This finding supports the existence of two distinct Roseolovirus lineages before the divergence of humans and macaques. Using specific qPCR assays, high levels of MneHV-6 and MneHV-7 DNA were detected in macaque saliva, although the frequency was greater for MneHV-7. A blood screen of 283 macaques revealed 10% MneHV-6 DNA positivity and 25% MneHV-7 positivity, with higher prevalences of MneHV-6 in older females and of MneHV-7 in younger males. Levels of MneHV-6 were increased in animals coinfected with MneHV-7, and both viruses were frequently detected in salivary gland and stomach tissues. Our discovery provides a unique animal model to answer unresolved questions regarding Roseolovirus pathology.
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