Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice
Despite the availability of anti-retroviral therapy, HIV-1 infection remains a massive burden on healthcare systems. Bacillus Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis, confers protection against meningitis and miliary tuberculosis in infants. Recombinant BCG has...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/7/3/78 |
| _version_ | 1811299565455802368 |
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| author | Athina Kilpeläinen Narcís Saubi Núria Guitart Alex Olvera Tomáš Hanke Christian Brander Joan Joseph |
| author_facet | Athina Kilpeläinen Narcís Saubi Núria Guitart Alex Olvera Tomáš Hanke Christian Brander Joan Joseph |
| author_sort | Athina Kilpeläinen |
| collection | DOAJ |
| description | Despite the availability of anti-retroviral therapy, HIV-1 infection remains a massive burden on healthcare systems. Bacillus Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis, confers protection against meningitis and miliary tuberculosis in infants. Recombinant BCG has been used as a vaccine vehicle to express both HIV-1 and Simian Immunodeficiemcy Virus (SIV) immunogens. In this study, we constructed an integrative <i>E. coli</i>-mycobacterial shuttle plasmid, p2auxo.HTI.int, expressing the HIVACAT T-cell immunogen (HTI). The plasmid was transformed into a lysine auxotrophic <i>Mycobacterium bovis</i> BCG strain (BCG<i>ΔLys</i>) to generate the vaccine BCG.HTI<sup>2auxo.int</sup>. The DNA sequence coding for the HTI immunogen and HTI protein expression were confirmed, and working vaccine stocks were genetically and phenotypically characterized. We demonstrated that the vaccine was stable in vitro for 35 bacterial generations, and that when delivered in combination with chimpanzee adenovirus (ChAd)Ox1.HTI in adult BALB/c mice, it was well tolerated and induced HIV-1-specific T-cell responses. Specifically, priming with BCG.HTI<sup>2auxo.int</sup> doubled the magnitude of the T-cell response in comparison with ChAdOx1.HTI alone while maintaining its breadth. The use of integrative expression vectors and novel HIV-1 immunogens can aid in improving mycobacterial vaccine stability as well as specific immunogenicity. This vaccine candidate may be a useful tool in the development of an effective vaccine platform for priming protective responses against HIV-1/TB and other prevalent pediatric pathogens. |
| first_indexed | 2024-04-13T06:37:44Z |
| format | Article |
| id | doaj.art-a36b8b1a9cfd4916bbdb73f2ea4d7c37 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-13T06:37:44Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-a36b8b1a9cfd4916bbdb73f2ea4d7c372022-12-22T02:57:50ZengMDPI AGVaccines2076-393X2019-08-01737810.3390/vaccines7030078vaccines7030078Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c MiceAthina Kilpeläinen0Narcís Saubi1Núria Guitart2Alex Olvera3Tomáš Hanke4Christian Brander5Joan Joseph6Catalan Center for HIV Vaccine Research and Development, AIDS Research Unit, Infectious Diseases Department, Hospital Clínic/IDIBAPS, 08036 Barcelona, Catalonia, SpainCatalan Center for HIV Vaccine Research and Development, AIDS Research Unit, Infectious Diseases Department, Hospital Clínic/IDIBAPS, 08036 Barcelona, Catalonia, SpainCatalan Center for HIV Vaccine Research and Development, AIDS Research Unit, Infectious Diseases Department, Hospital Clínic/IDIBAPS, 08036 Barcelona, Catalonia, SpainIrsicaixa AIDS Research Institute, 08916 Badalona, Catalonia, SpainNuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKIrsicaixa AIDS Research Institute, 08916 Badalona, Catalonia, SpainCatalan Center for HIV Vaccine Research and Development, AIDS Research Unit, Infectious Diseases Department, Hospital Clínic/IDIBAPS, 08036 Barcelona, Catalonia, SpainDespite the availability of anti-retroviral therapy, HIV-1 infection remains a massive burden on healthcare systems. Bacillus Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis, confers protection against meningitis and miliary tuberculosis in infants. Recombinant BCG has been used as a vaccine vehicle to express both HIV-1 and Simian Immunodeficiemcy Virus (SIV) immunogens. In this study, we constructed an integrative <i>E. coli</i>-mycobacterial shuttle plasmid, p2auxo.HTI.int, expressing the HIVACAT T-cell immunogen (HTI). The plasmid was transformed into a lysine auxotrophic <i>Mycobacterium bovis</i> BCG strain (BCG<i>ΔLys</i>) to generate the vaccine BCG.HTI<sup>2auxo.int</sup>. The DNA sequence coding for the HTI immunogen and HTI protein expression were confirmed, and working vaccine stocks were genetically and phenotypically characterized. We demonstrated that the vaccine was stable in vitro for 35 bacterial generations, and that when delivered in combination with chimpanzee adenovirus (ChAd)Ox1.HTI in adult BALB/c mice, it was well tolerated and induced HIV-1-specific T-cell responses. Specifically, priming with BCG.HTI<sup>2auxo.int</sup> doubled the magnitude of the T-cell response in comparison with ChAdOx1.HTI alone while maintaining its breadth. The use of integrative expression vectors and novel HIV-1 immunogens can aid in improving mycobacterial vaccine stability as well as specific immunogenicity. This vaccine candidate may be a useful tool in the development of an effective vaccine platform for priming protective responses against HIV-1/TB and other prevalent pediatric pathogens.https://www.mdpi.com/2076-393X/7/3/78BCGHIVvaccinerBCGHTIT-cell |
| spellingShingle | Athina Kilpeläinen Narcís Saubi Núria Guitart Alex Olvera Tomáš Hanke Christian Brander Joan Joseph Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice Vaccines BCG HIV vaccine rBCG HTI T-cell |
| title | Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice |
| title_full | Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice |
| title_fullStr | Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice |
| title_full_unstemmed | Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice |
| title_short | Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice |
| title_sort | recombinant bcg expressing hti prime and recombinant chadox1 boost is safe and elicits hiv 1 specific t cell responses in balb c mice |
| topic | BCG HIV vaccine rBCG HTI T-cell |
| url | https://www.mdpi.com/2076-393X/7/3/78 |
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