A Simian Replication-Defective Adenoviral Recombinant Vaccine to HIV-1 Gag

Abstract

In animal models, E1-deleted human adenoviral recombinants of the serotype 5 (AdHu5) have shown high efficacy as vaccine carriers for different Ags including those of HIV-1. Humans are infected by common serotypes of human adenovirus such as AdHu5 early in life and a significant percentage has high levels of neutralizing Abs to these serotypes, which will very likely impair the efficacy of recombinant vaccines based on the homologous virus. To circumvent this problem, a novel replication-defective adenoviral vaccine carrier based on an E1-deleted recombinant of the chimpanzee adenovirus 68 (AdC68) was developed. An AdC68 construct expressing a codon-optimized, truncated form of gag of HIV-1 induces CD8+ T cells to gag in mice which at the height of the immune response encompass nearly 20% of the entire splenic CD8+ T cell population. The vaccine-induced immune response provides protection to challenge with a vaccinia gag recombinant virus. Induction of transgene-specific CD8+ T cells and protection against viral challenge elicited by the AdC68 vaccines is not strongly inhibited in animals preimmune to AdHu5 virus. However, the response elicited by the AdHu5 vaccine is greatly attenuated in AdHu5 preimmune animals.

Efficient induction of T‐cell responses to carcinoembryonic antigen by a heterologous prime‐boost regimen using DNA and adenovirus vectors carrying a codon usage optimized cDNA

“…Finally, it has been reported that injection of Ad vectors is likely to induce neutralizing antibodies to the virus, thereby hampering its immunogenic efficiency. 46,47 Indeed, we have detected high titers of Ad neutralizing antibodies in the transgenic mice after Ad injection that have a detrimental effect on the immunogenicity of subsequent Ad injections. However, unlike Ad, plasmid DNA injection can fully boost the T-cell response elicited by Ad injection (data not shown).…”

Intramuscular rather than oral administration of replication-defective adenoviral vaccine vector induces specific CD8+ T cell responses in the gut

“…Chimpanzee adenoviral vectors have been shown to elicit strong CD8 + T cell responses to transgene products [13]; however, it is unknown whether oral vaccination with these vectors induces mucosal CD8 + T cells including in animals with pre-existing immunity to a common human adenovirus serotype. Here we tested the intestinal mucosal responses to oral and intramuscular (i.m.)…”

Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules

“…While attenuation of IgA responses was eventually observed, the ability to immunize multiple times appears effective as a priming regimen for other vaccines or for the use of other serotypes of Ad [59][60][61][62]. Proof of principle is demonstrated here where mucosal oral priming of macaques by oral Ad administration was followed by mucosal boosting with an intranasal peptide vaccine.…”