Highly Effective Control of an AIDS Virus Challenge in Macaques by Using Vesicular Stomatitis Virus and Modified Vaccinia Virus Ankara Vaccine Vectors in a Single-Boost Protocol

Abstract

Previous studies have shown that vaccination and boosting of rhesus macaques with attenuated vesicular stomatitis virus (VSV) vectors encoding Env and Gag proteins of simian immunodeficiency virus-human immunodeficiency virus (SHIV) hybrid viruses protect rhesus macaques from AIDS after challenge with the highly pathogenic SHIV 89.6P (23). In the present study, we compared the effectiveness of a single prime-boost protocol consisting of VSV vectors expressing SHIV Env, Gag, and Pol proteins to that of a protocol consisting of a VSV vector prime followed with a single boost with modified vaccinia virus Ankara (MVA) expressing the same SHIV proteins. After challenge with SHIV 89.6P, MVA-boosted animals controlled peak challenge viral loads to less than 2 ؋ 10 6 copies/ml (a level significantly lower than that seen with VSV-boosted animals and lower than those reported for other vaccine studies employing the same challenge). MVA-boosted animals have shown excellent preservation of CD4 ؉ T cells, while two of four VSV-boosted animals have shown significant loss of CD4 ؉ T cells. The improved protection in MVA-boosted animals correlates with trends toward stronger prechallenge CD8؉ -T-cell responses to SHIV antigens and stronger postchallenge SHIV-neutralizing antibody production.

Generation and evaluation of a recombinant modified vaccinia virus Ankara vaccine for rabies

“…This finding appears to be in line with others, such as a study involving recombinant MVA expressing measles virus antigens, where MVA recombinants boosted low-levels of vaccine induced immunity much more efficiently than live attenuated measles virus vaccine [64]. Booster responses induced by MVA recombinants upon mucosal delivery, specifically after intranasal delivery, have also been indicated in macaques [65] and [66]. The most prominent value of recombinant MVA vaccines lie in this so-called "booster effect".…”

Chimpanzee-origin adenovirus vectors as vaccine carriers

“…A number of different vaccine carriers have been tested preclinically as well as in part clinically for induction of CD8 + T-cell responses to HIV-1. [28][29][30][31][32][33] Here we compared simian Ad vectors that varied with regard to deletions and insert lengths to determine which types of constructs are most suitable for further clinical development. DE1AdC68 and DE1/E3AdC68 vectors showed favorable growth characteristics and yields commonly exceeded those of AdHu5 vectors.…”

Vaccine-Induced, Simian Immunodeficiency Virus-Specific CD8+ T Cells Reduce Virus Replication but Do Not Protect from Simian Immunodeficiency Virus Disease Progression

“…A number of vector platforms, including plasmid DNA, adenovirus (Ad), 4 modified vaccinia Ankara (MVA), vescicular stomatitis virus, and various others have shown some protection from subsequent pathogenic challenge in rhesus macaques (RM; Refs. [10][11][12][13][14]. However, these immunization protocols were mainly successful against the chimeric SHIV89.6P viral strain the relevance of which as a challenge model is questionable (15).…”