Immunogenicity and protection against Mycobacterium avium with a heterologous RNA prime and protein boost vaccine regimen

• Published in: Tuberculosis (Edinburgh, Scotland) Scotland), 2023-01, Vol.138, p.102302-102302, Article 102302
• Main Authors: Rais, Maham, Abdelaal, Hazem, Reese, Valerie A., Ferede, Debora, Larsen, Sasha E., Pecor, Tiffany, Erasmus, Jesse H., Archer, Jacob, Khandhar, Amit P., Cooper, Sarah K., Podell, Brendan K., Reed, Steven G., Coler, Rhea N., Baldwin, Susan L.
• Format: Article
• Language: English
• Subjects: Animals; CD8-Positive T-Lymphocytes; Cytokines - metabolism; Immunization, Secondary - methods; Mice; Mycobacterium avium - metabolism; Mycobacterium tuberculosis - genetics; Vaccination - methods; Vaccines, DNA
• ISSN: 1472-9792; 1873-281X; 1873-281X
• DOI: 10.1016/j.tube.2022.102302

Prophylactic efficacy of two different delivery platforms for vaccination against Mycobacterium avium (M. avium) were tested in this study; a subunit and an RNA-based vaccine. The vaccine antigen, ID91, includes four mycobacterial antigens: Rv3619, Rv2389, Rv3478, and Rv1886. We have shown that ID91+GLA-SE is effective against a clinical NTM isolate, M. avium 2–151 smt. Here, we extend these results and show that a heterologous prime/boost strategy with a repRNA-ID91 (replicon RNA) followed by protein ID91+GLA-SE boost is superior to the subunit protein vaccine given as a homologous prime/boost regimen. The repRNA-ID91/ID91+GLA-SE heterologous regimen elicited a higher polyfunctional CD4+ TH1 immune response when compared to the homologous protein prime/boost regimen. More significantly, among all the vaccine regimens tested only repRNA-ID91/ID91+GLA-SE induced IFN-γ and TNF-secreting CD8+ T cells. Furthermore, the repRNA-ID91/ID91+GLA-SE vaccine strategy elicited high systemic proinflammatory cytokine responses and induced strong ID91 and an Ag85B-specific humoral antibody response a pre- and post-challenge with M. avium 2–151 smt. Finally, while all prophylactic prime/boost vaccine regimens elicited a degree of protection in beige mice, the heterologous repRNA-ID91/ID91+GLA-SE vaccine regimen provided greater pulmonary protection than the homologous protein prime/boost regimen. These data indicate that a prophylactic heterologous repRNA-ID91/ID91+GLA-SE vaccine regimen augments immunogenicity and confers protection against M. avium.