Antibody-Mediated Protection against Mucosal Simian-Human Immunodeficiency Virus Challenge of Macaques Immunized with Alphavirus Replicon Particles and Boosted with Trimeric Envelope Glycoprotein in MF59 Adjuvant
Open accessAbstract
We have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus SHIV SF162P4 following sequential immunization with alpha v irus r eplicon p articles (VRP) of a chimeric recombinant VEE/SIN alphavirus (derived from Venezuelan equine encephalitis virus [VEE] and the Sindbis virus [SIN]) encoding human immunodeficiency virus type 1 HIV-1 SF162 gp140ΔV2 envelope (Env) and trimeric Env protein in MF59 adjuvant (R. Xu, I. K. Srivastava, C. E. Greer, I. Zarkikh, Z. Kraft, L. Kuller, J. M. Polo, S. W. Barnett, and L. Stamatatos, AIDS Res. Hum. Retroviruses 22:1022-1030, 2006). The protection did not require T-cell immune responses directed toward simian immunodeficiency virus (SIV) Gag. We extend those findings here to demonstrate antibody-mediated protection against mucosal challenge in macaques using prime-boost regimens incorporating both intramuscular and mucosal routes of delivery. The macaques in the vaccination groups were primed with VRP and then boosted with Env protein in MF59 adjuvant, or they were given VRP intramuscular immunizations alone and then challenged with SHIV SF162P4 (intrarectal challenge). The results demonstrated that these vaccines were able to effectively protect the macaques to different degrees against subsequent mucosal SHIV challenge, but most noteworthy, all macaques that received the intramuscular VRP prime plus Env protein boost were completely protected. A statistically significant association was observed between the titer of virus neutralizing and binding antibodies as well as the avidity of anti-Env antibodies measured prechallenge and protection from infection. These results highlight the merit of the alphavirus replicon vector prime plus Env protein boost vaccine approach for the induction of protective antibody responses and are of particular relevance to advancing our understanding of the potential correlates of immune protection against HIV infection at a relevant mucosal portal of entry.
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VRPs are potent vaccines in mice, nonhuman primates, and humans.
“VRPs are potent vaccines in mice (10,11), nonhuman primates (11,22), and humans (25).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [22]
The Discussion (page unavailable) reports complete protection of rhesus macaques given an intramuscular VRP prime plus Env-protein boost, supporting the nonhuman-primate portion attributed to this source. It also says none of the macaques given VRP alone were protected, so the unqualified description of VRPs as potent vaccines overstates this study. The separate mice and humans citations are not being judged here. (LLM, conf=0.85)
Experimental — accuracy not yet measuredVRPs have been shown to be potent in nonhuman primates and humans at a 100-fold higher dose (1 × 10^8 IU).
“VRPs have been shown to be potent in nonhuman primates and humans at a 100-fold higher dose (1 × 10 8 IU) (22,25), and thus we anticipate that this unique RNA vaccine will be immunogenic at submilligram doses in larger species, but this remains to be directly tested.”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [22]
Materials and Methods reports a VRP dose of 1 × 10^8 IU in rhesus macaques, and the Results and Discussion report immune responses and protection with a VRP-prime/Env-protein-boost regimen. The copy does not establish potency in humans or that this dose was 100-fold higher than a comparison dose; it also reports that VRP alone did not protect the macaques. (LLM, conf=0.86)
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- Authors
- Barnett, S. W., Burke, B., Sun, Y., Kan, E., Legg, H., Lian, Y., Bost, K., Zhou, F., Goodsell, A., zur Megede, J., Polo, J., Donnelly, J., Ulmer, J., Otten, G. R., Miller, C. J., Vajdy, M., & Srivastava, I. K.
- Affiliations
- Novartis (United States) (US)
- University of California, Davis (US)
- Novartis Vaccines and Diagnostics, 350 Massachusetts Avenue, Cambridge, Massachusetts 02139
- Corresponding author
- Barnett, Susan W.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2010-06-15
- Volume
- 84
- Issue
- 12
- Pages
- 5975-5985
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2876657
- OpenAlex
- W2130651219
- Cited by
- 82
- References
- 62
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 8 · 2014: 13 · 2013: 13 · 2012: 14
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01ai50007-7-0-1)
- U.S. Public Health Service
- National Institute of Allergy and Infectious Diseases (U19AI51596, U19AI051596, 1 U19 AI51596, N01 AI050007, P01AI066287)
- National Center for Research Resources (P51RR000169, U51 RR00169)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1 vaccine, MF59 adjuvant, mucosal challenge, intrarectal challenge, antibody-mediated protection, virus-neutralizing antibodies, prime-boost vaccination, rhesus monkeys, HIV-1 envelope glycoprotein
- MeSH terms
- Adjuvants, Immunologic, Alphavirus, Animals, Antibodies, Viral, Cell Line, Disease Models, Animal, Humans, Immunization, Macaca, Male, Polysorbates, Replicon, Squalene, Simian Immunodeficiency Virus, HIV-1, HIV Infections, AIDS Vaccines, env Gene Products, Human Immunodeficiency Virus
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