Safety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boost
Abstract Developing a safe and effective vaccine remains a global priority for ending the human immunodeficiency virus (HIV) pandemic. All HIV vaccine trials with protein, DNA, non-replication vector or their combinations failed in the past. We constructed the HIV-1 CN54 env, gag, and pol genes into...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02259-y |
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| author | Ying Liu Wei Lv Pu Shan Dan Li Ying-Qi Wu You-Chun Wang Yuan-Yuan Li Qiang Liu Jian-Sheng Wang Yan-Ling Hao Yong Liu Wei-Jin Huang Li Ren Shu-Hui Wang Tai-Sheng Li Jing Xu Yi-Ming Shao |
| author_facet | Ying Liu Wei Lv Pu Shan Dan Li Ying-Qi Wu You-Chun Wang Yuan-Yuan Li Qiang Liu Jian-Sheng Wang Yan-Ling Hao Yong Liu Wei-Jin Huang Li Ren Shu-Hui Wang Tai-Sheng Li Jing Xu Yi-Ming Shao |
| author_sort | Ying Liu |
| collection | DOAJ |
| description | Abstract Developing a safe and effective vaccine remains a global priority for ending the human immunodeficiency virus (HIV) pandemic. All HIV vaccine trials with protein, DNA, non-replication vector or their combinations failed in the past. We constructed the HIV-1 CN54 env, gag, and pol genes into both DNA and replicating vaccinia virus Tiantan vectors. In phase Ia, 12 healthy adults were given high (n = 6) or low (n = 6) doses of recombinant vaccinia virus Tiantan vaccine (rTV), to test its safety dose. In phase Ib, 36 healthy adults were assigned to the DNA (n = 6), DNA-L/rTV (n = 12), DNA-H/rTV (n = 12), and placebo (n = 6) groups. The DNA vaccine was injected intramuscularly at weeks 0, 4, and 8 and rTV with a bifurcated needle at week 12. All vaccines tested were safe and well-tolerated; most of the adverse events (AEs) were mild to moderate. The most commonly observed AEs were redness and papule at rTV vaccination sites and axillary enlarged lymph nodes at the same rTV vaccination arm. Smaller cutaneous lesions and shorter healing time were observed in smallpox vaccine experienced subjects. The DNA prime-rTV boost regimen induced anti-gp120 IgG and polyfunctional CD4+ T cells. No significant differences of anti-HIV IgG and T cell responses were found between the two prime-boost groups with high and low DNA doses. Moreover, smallpox vaccine naïve subjects elicited higher T cell responses and anti-gp120 antibodies. The result of this trial supports further development of HIV vaccine with DNA and replicating vaccinia vector for advanced clinical trials. |
| format | Article |
| id | doaj-art-e0811cfffed6466fa3fd564990edf6e0 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-e0811cfffed6466fa3fd564990edf6e02025-08-20T03:45:41ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-07-0110111010.1038/s41392-025-02259-ySafety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boostYing Liu0Wei Lv1Pu Shan2Dan Li3Ying-Qi Wu4You-Chun Wang5Yuan-Yuan Li6Qiang Liu7Jian-Sheng Wang8Yan-Ling Hao9Yong Liu10Wei-Jin Huang11Li Ren12Shu-Hui Wang13Tai-Sheng Li14Jing Xu15Yi-Ming Shao16National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and PreventionDepartment of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesNational Vaccine & Serum InstituteNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and PreventionNational Institutes for Food and Drug ControlNational Vaccine & Serum InstituteNational Institutes for Food and Drug ControlDivision of Health Statistics, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and PreventionNational Institutes for Food and Drug ControlNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and PreventionNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and PreventionDepartment of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesNational Vaccine & Serum InstituteNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and PreventionAbstract Developing a safe and effective vaccine remains a global priority for ending the human immunodeficiency virus (HIV) pandemic. All HIV vaccine trials with protein, DNA, non-replication vector or their combinations failed in the past. We constructed the HIV-1 CN54 env, gag, and pol genes into both DNA and replicating vaccinia virus Tiantan vectors. In phase Ia, 12 healthy adults were given high (n = 6) or low (n = 6) doses of recombinant vaccinia virus Tiantan vaccine (rTV), to test its safety dose. In phase Ib, 36 healthy adults were assigned to the DNA (n = 6), DNA-L/rTV (n = 12), DNA-H/rTV (n = 12), and placebo (n = 6) groups. The DNA vaccine was injected intramuscularly at weeks 0, 4, and 8 and rTV with a bifurcated needle at week 12. All vaccines tested were safe and well-tolerated; most of the adverse events (AEs) were mild to moderate. The most commonly observed AEs were redness and papule at rTV vaccination sites and axillary enlarged lymph nodes at the same rTV vaccination arm. Smaller cutaneous lesions and shorter healing time were observed in smallpox vaccine experienced subjects. The DNA prime-rTV boost regimen induced anti-gp120 IgG and polyfunctional CD4+ T cells. No significant differences of anti-HIV IgG and T cell responses were found between the two prime-boost groups with high and low DNA doses. Moreover, smallpox vaccine naïve subjects elicited higher T cell responses and anti-gp120 antibodies. The result of this trial supports further development of HIV vaccine with DNA and replicating vaccinia vector for advanced clinical trials.https://doi.org/10.1038/s41392-025-02259-y |
| spellingShingle | Ying Liu Wei Lv Pu Shan Dan Li Ying-Qi Wu You-Chun Wang Yuan-Yuan Li Qiang Liu Jian-Sheng Wang Yan-Ling Hao Yong Liu Wei-Jin Huang Li Ren Shu-Hui Wang Tai-Sheng Li Jing Xu Yi-Ming Shao Safety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boost Signal Transduction and Targeted Therapy |
| title | Safety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boost |
| title_full | Safety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boost |
| title_fullStr | Safety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boost |
| title_full_unstemmed | Safety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boost |
| title_short | Safety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boost |
| title_sort | safety and immunogenicity of an hiv vaccine trial with dna prime and replicating vaccinia boost |
| url | https://doi.org/10.1038/s41392-025-02259-y |
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