herpesvirus vector
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2021 ◽  
Author(s):  
Isabelle M. Castro ◽  
Michael J. Ricciardi ◽  
Lucas Gonzalez-Nieto ◽  
Eva G. Rakasz ◽  
Jeffrey D. Lifson ◽  
...  

A prophylactic vaccine that confers durable protection against human immunodeficiency virus (HIV) would provide a valuable tool to prevent new HIV/AIDS cases. As herpesviruses establish lifelong infections that remain largely subclinical, the use of persistent herpesvirus vectors to deliver HIV antigens may facilitate the induction of long-term anti-HIV immunity. We previously developed recombinant (r) forms of the gamma-herpesvirus rhesus monkey rhadinovirus (rRRV) expressing a replication-incompetent, near-full-length simian immunodeficiency virus (SIVnfl) genome. We recently showed that 8/16 rhesus macaques (RMs) vaccinated with a rDNA/rRRV-SIVnfl regimen were significantly protected against intrarectal (IR) challenge with SIVmac239. Here we investigated the longevity of this vaccine-mediated protection. Despite receiving no additional booster immunizations, the protected rDNA/rRRV-SIVnfl vaccinees maintained detectable cellular and humoral anti-SIV immune responses for more than 1.5 years after the rRRV boost. To assess if these responses were still protective, the rDNA/rRRV-SIVnfl vaccinees were subjected to a second round of marginal-dose IR SIVmac239 challenges, with eight SIV-naïve RMs serving as concurrent controls. After three SIV exposures, 8/8 control animals became infected, compared to 3/8 vaccinees. This difference in SIV acquisition was statistically significant (P = 0.0035). The three vaccinated monkeys that became infected exhibited significantly lower viral loads than those in unvaccinated controls. Collectively, these data illustrate the ability of rDNA/rRRV-SIVnfl vaccination to provide long-term immunity against stringent mucosal challenges with SIVmac239. Future work is needed to identify the critical components of this vaccine-mediated protection and the extent to which it can tolerate sequence mismatches in the challenge virus. IMPORTANCE We report on the long-term follow-up of a group of rhesus macaques (RMs) that received an AIDS vaccine regimen and were subsequently protected against rectal acquisition of simian immunodeficiency virus (SIV) infection. The vaccination regimen employed included a live recombinant herpesvirus vector that establishes persistent infection in RMs. Consistent with the recurrent SIV antigen expression afforded by this herpesvirus vector, vaccinees maintained detectable SIV-specific immune responses for more than 1.5 years after the last vaccination. Importantly, these vaccinated RMs were significantly protected against a second round of rectal SIV exposures performed one year after the first SIV challenge phase. These results are relevant for HIV vaccine development because they show the potential of herpesvirus-based vectors to maintain functional antiretroviral immunity without the need for repeated boosting.


2018 ◽  
Vol 63 (1) ◽  
pp. 75 ◽  
Author(s):  
John R. Dunn ◽  
Kiril M. Dimitrov ◽  
Patti J. Miller ◽  
Maricarmen Garcia ◽  
Kelly Turner-Alston ◽  
...  

Author(s):  
Atsushi Yasuda ◽  
Motoyuki Esaki ◽  
Kristi Moore Dorsey ◽  
Zoltan Penzes ◽  
Vilmos Palya ◽  
...  

2014 ◽  
Vol 158 (1-2) ◽  
pp. 105-115 ◽  
Author(s):  
Vilmos Palya ◽  
Tímea Tatár-Kis ◽  
Tamás Mató ◽  
Balázs Felföldi ◽  
Edit Kovács ◽  
...  

2013 ◽  
Vol 57 (4) ◽  
pp. 750-755 ◽  
Author(s):  
Motoyuki Esaki ◽  
Alecia Godoy ◽  
Jack K. Rosenberger ◽  
Sandra C. Rosenberger ◽  
Yannick Gardin ◽  
...  

2013 ◽  
Vol 57 (2) ◽  
pp. 192-198 ◽  
Author(s):  
Motoyuki Esaki ◽  
Lauren Noland ◽  
Tim Eddins ◽  
Alecia Godoy ◽  
Sakiko Saeki ◽  
...  

2000 ◽  
Vol 30 (11) ◽  
pp. 1167-1171 ◽  
Author(s):  
Yoshifumi Nishikawa ◽  
Hiroyasu Ikeda ◽  
Shiya Fukumoto ◽  
Xuenan Xuan ◽  
Hideyuki Nagasawa ◽  
...  

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