Enhancement of Neutralization Responses through Sequential Immunization of Stable Env Trimers Based on Consensus Sequences from Select Time Points by Mimicking Natural Infection
HIV-1 vaccines have been challenging to develop, partly due to the high level of genetic variation in its genome. Thus, a vaccine that can induce cross-reactive neutralization activities will be needed. Studies on the co-evolution of antibodies and viruses indicate that mimicking the natural infecti...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12642 |
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| author | Mingming Wan Xiao Yang Jie Sun Elena E. Giorgi Xue Ding Yan Zhou Yong Zhang Weiheng Su Chunlai Jiang Yaming Shan Feng Gao |
| author_facet | Mingming Wan Xiao Yang Jie Sun Elena E. Giorgi Xue Ding Yan Zhou Yong Zhang Weiheng Su Chunlai Jiang Yaming Shan Feng Gao |
| author_sort | Mingming Wan |
| collection | DOAJ |
| description | HIV-1 vaccines have been challenging to develop, partly due to the high level of genetic variation in its genome. Thus, a vaccine that can induce cross-reactive neutralization activities will be needed. Studies on the co-evolution of antibodies and viruses indicate that mimicking the natural infection is likely to induce broadly neutralizing antibodies (bnAbs). We generated the consensus Env sequence for each time point in subject CH505, who developed broad neutralization activities, and selected five critical time points before broad neutralization was detected. These consensus sequences were designed to express stable Env trimers. Priming with the transmitted/founder Env timer and sequential boosting with these consensus Env trimers from different time points induced broader and more potent neutralizing activities than the BG505 Env trimer in guinea pigs. Analysis of the neutralization profiles showed that sequential immunization of Env trimers favored nAbs with gp120/gp41 interface specificity while the BG505 Env trimer favored nAbs with V2 specificity. The unique features such as consensus sequences, stable Env trimers and the sequential immunization to mimic natural infection likely has allowed the induction of improved neutralization responses. |
| first_indexed | 2024-03-10T23:52:57Z |
| format | Article |
| id | doaj.art-fa55a42be2e74f899efc0d28201af523 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:52:57Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fa55a42be2e74f899efc0d28201af5232023-11-19T01:26:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161264210.3390/ijms241612642Enhancement of Neutralization Responses through Sequential Immunization of Stable Env Trimers Based on Consensus Sequences from Select Time Points by Mimicking Natural InfectionMingming Wan0Xiao Yang1Jie Sun2Elena E. Giorgi3Xue Ding4Yan Zhou5Yong Zhang6Weiheng Su7Chunlai Jiang8Yaming Shan9Feng Gao10National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USANational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, ChinaHIV-1 vaccines have been challenging to develop, partly due to the high level of genetic variation in its genome. Thus, a vaccine that can induce cross-reactive neutralization activities will be needed. Studies on the co-evolution of antibodies and viruses indicate that mimicking the natural infection is likely to induce broadly neutralizing antibodies (bnAbs). We generated the consensus Env sequence for each time point in subject CH505, who developed broad neutralization activities, and selected five critical time points before broad neutralization was detected. These consensus sequences were designed to express stable Env trimers. Priming with the transmitted/founder Env timer and sequential boosting with these consensus Env trimers from different time points induced broader and more potent neutralizing activities than the BG505 Env trimer in guinea pigs. Analysis of the neutralization profiles showed that sequential immunization of Env trimers favored nAbs with gp120/gp41 interface specificity while the BG505 Env trimer favored nAbs with V2 specificity. The unique features such as consensus sequences, stable Env trimers and the sequential immunization to mimic natural infection likely has allowed the induction of improved neutralization responses.https://www.mdpi.com/1422-0067/24/16/12642HIV-1vaccinesequential immunizationconsensusEnv trimers |
| spellingShingle | Mingming Wan Xiao Yang Jie Sun Elena E. Giorgi Xue Ding Yan Zhou Yong Zhang Weiheng Su Chunlai Jiang Yaming Shan Feng Gao Enhancement of Neutralization Responses through Sequential Immunization of Stable Env Trimers Based on Consensus Sequences from Select Time Points by Mimicking Natural Infection International Journal of Molecular Sciences HIV-1 vaccine sequential immunization consensus Env trimers |
| title | Enhancement of Neutralization Responses through Sequential Immunization of Stable Env Trimers Based on Consensus Sequences from Select Time Points by Mimicking Natural Infection |
| title_full | Enhancement of Neutralization Responses through Sequential Immunization of Stable Env Trimers Based on Consensus Sequences from Select Time Points by Mimicking Natural Infection |
| title_fullStr | Enhancement of Neutralization Responses through Sequential Immunization of Stable Env Trimers Based on Consensus Sequences from Select Time Points by Mimicking Natural Infection |
| title_full_unstemmed | Enhancement of Neutralization Responses through Sequential Immunization of Stable Env Trimers Based on Consensus Sequences from Select Time Points by Mimicking Natural Infection |
| title_short | Enhancement of Neutralization Responses through Sequential Immunization of Stable Env Trimers Based on Consensus Sequences from Select Time Points by Mimicking Natural Infection |
| title_sort | enhancement of neutralization responses through sequential immunization of stable env trimers based on consensus sequences from select time points by mimicking natural infection |
| topic | HIV-1 vaccine sequential immunization consensus Env trimers |
| url | https://www.mdpi.com/1422-0067/24/16/12642 |
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