Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates
The search for a preventive vaccine against HIV infection remains an ongoing challenge, indicating the need for novel approaches. Parainfluenza virus 5 (PIV5) is a paramyxovirus replicating in the upper airways that is not associated with any animal or human pathology. In animal models, PIV5-vectore...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.623996/full |
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| author | Peng Xiao Krista Dienger-Stambaugh Xuemin Chen Huiling Wei Shannon Phan Ashley C. Beavis Karnail Singh Nihar R. Deb Adhikary Pooja Tiwari Francois Villinger Biao He Paul Spearman |
| author_facet | Peng Xiao Krista Dienger-Stambaugh Xuemin Chen Huiling Wei Shannon Phan Ashley C. Beavis Karnail Singh Nihar R. Deb Adhikary Pooja Tiwari Francois Villinger Biao He Paul Spearman |
| author_sort | Peng Xiao |
| collection | DOAJ |
| description | The search for a preventive vaccine against HIV infection remains an ongoing challenge, indicating the need for novel approaches. Parainfluenza virus 5 (PIV5) is a paramyxovirus replicating in the upper airways that is not associated with any animal or human pathology. In animal models, PIV5-vectored vaccines have shown protection against influenza, RSV, and other human pathogens. Here, we generated PIV5 vaccines expressing HIV envelope (Env) and SIV Gag and administered them intranasally to macaques, followed by boosting with virus-like particles (VLPs) containing trimeric HIV Env. Moreover, we compared the immune responses generated by PIV5-SHIV prime/VLPs boost regimen in naïve vs a control group in which pre-existing immunity to the PIV5 vector was established. We demonstrate for the first time that intranasal administration of PIV5-based HIV vaccines is safe, well-tolerated and immunogenic, and that boosting with adjuvanted trimeric Env VLPs enhances humoral and cellular immune responses. The PIV5 prime/VLPs boost regimen induced robust and durable systemic and mucosal Env-specific antibody titers with functional activities including ADCC and neutralization. This regimen also induced highly polyfunctional antigen-specific T cell responses. Importantly, we show that diminished responses due to PIV5 pre-existing immunity can be overcome in part with VLP protein boosts. Overall, these results establish that PIV5-based HIV vaccine candidates are promising and warrant further investigation including moving on to primate challenge studies. |
| first_indexed | 2024-12-14T17:11:27Z |
| format | Article |
| id | doaj.art-0812cea0affa41828faa00f55fffe1ef |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T17:11:27Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0812cea0affa41828faa00f55fffe1ef2022-12-21T22:53:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011210.3389/fimmu.2021.623996623996Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman PrimatesPeng Xiao0Krista Dienger-Stambaugh1Xuemin Chen2Huiling Wei3Shannon Phan4Ashley C. Beavis5Karnail Singh6Nihar R. Deb Adhikary7Pooja Tiwari8Francois Villinger9Biao He10Paul Spearman11New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United StatesDivision of Infectious Diseases, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH, United StatesDivision of Infectious Diseases, Emory University, Atlanta, GA, United StatesDepartment of Infectious Diseases, University of Georgia, Athens, GA, United StatesDepartment of Infectious Diseases, University of Georgia, Athens, GA, United StatesDepartment of Infectious Diseases, University of Georgia, Athens, GA, United StatesDivision of Infectious Diseases, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH, United StatesNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United StatesWallace H Coulter Department of Bioengineering, Georgia Institute of Technology, Atlanta, GA, United StatesNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United StatesDepartment of Infectious Diseases, University of Georgia, Athens, GA, United StatesDivision of Infectious Diseases, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH, United StatesThe search for a preventive vaccine against HIV infection remains an ongoing challenge, indicating the need for novel approaches. Parainfluenza virus 5 (PIV5) is a paramyxovirus replicating in the upper airways that is not associated with any animal or human pathology. In animal models, PIV5-vectored vaccines have shown protection against influenza, RSV, and other human pathogens. Here, we generated PIV5 vaccines expressing HIV envelope (Env) and SIV Gag and administered them intranasally to macaques, followed by boosting with virus-like particles (VLPs) containing trimeric HIV Env. Moreover, we compared the immune responses generated by PIV5-SHIV prime/VLPs boost regimen in naïve vs a control group in which pre-existing immunity to the PIV5 vector was established. We demonstrate for the first time that intranasal administration of PIV5-based HIV vaccines is safe, well-tolerated and immunogenic, and that boosting with adjuvanted trimeric Env VLPs enhances humoral and cellular immune responses. The PIV5 prime/VLPs boost regimen induced robust and durable systemic and mucosal Env-specific antibody titers with functional activities including ADCC and neutralization. This regimen also induced highly polyfunctional antigen-specific T cell responses. Importantly, we show that diminished responses due to PIV5 pre-existing immunity can be overcome in part with VLP protein boosts. Overall, these results establish that PIV5-based HIV vaccine candidates are promising and warrant further investigation including moving on to primate challenge studies.https://www.frontiersin.org/articles/10.3389/fimmu.2021.623996/fullparainfluenza virus 5 (PIV5)human immunodeficiency virus (HIV) vaccinevirus-like particles (VLP)rhesus macaquesimmune responses |
| spellingShingle | Peng Xiao Krista Dienger-Stambaugh Xuemin Chen Huiling Wei Shannon Phan Ashley C. Beavis Karnail Singh Nihar R. Deb Adhikary Pooja Tiwari Francois Villinger Biao He Paul Spearman Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates Frontiers in Immunology parainfluenza virus 5 (PIV5) human immunodeficiency virus (HIV) vaccine virus-like particles (VLP) rhesus macaques immune responses |
| title | Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates |
| title_full | Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates |
| title_fullStr | Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates |
| title_full_unstemmed | Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates |
| title_short | Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates |
| title_sort | parainfluenza virus 5 priming followed by siv hiv virus like particle boosting induces potent and durable immune responses in nonhuman primates |
| topic | parainfluenza virus 5 (PIV5) human immunodeficiency virus (HIV) vaccine virus-like particles (VLP) rhesus macaques immune responses |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.623996/full |
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