Evaluation of antiviral T cell responses and T.sub.SCM cells in volunteers enrolled in a phase I HIV-1 subtype C prophylactic vaccine trial in India

• Published in: PloS one Vol. 15; no. 2; p. e0229461
• Main Authors: Munusamy Ponnan, Sivasankaran, Hayes, Peter, Fernandez, Natalia, Thiruvengadam, Kannan, Pattabiram, Sathyamurthi, Nesakumar, Manohar, Srinivasan, Ashokkumar, Kathirvel, Sujitha, Shankar, Janani, Goyal, Rajat, Singla, Nikhil, Mukherjee, Joyeeta, Chatrath, Shweta, Gilmour, Jill, Subramanyam, Sudha, Prasad Tripathy, Srikanth, Swaminathan, Soumya, Hanna, Luke Elizabeth, Ansari, Aftab A
• Format: Journal Article
• Language: English
• Published: Public Library of Science 25.02.2020
• Subjects: AIDS vaccines; Analysis; Biotechnology industries; Clinical trials; DNA; Drug therapy; Health aspects; HIV; HIV infections; Immune response; Infection; Medical research; Novels; Stem cells; T cells; Vaccination; Vaccines; Virus replication; United States; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0229461

T cells play an important role in controlling viral replication during HIV infection. An effective vaccine should, therefore, lead to the induction of a strong and early viral-specific CD8.sup.+ T cell response. While polyfunctional T cell responses are thought to be important contributors to the antiviral response, there is evidence to show that polyfunctional HIV- specific CD8.sup.+ T cells are just a small fraction of the total HIV-specific CD8.sup.+ T cells and may be absent in many individuals who control HIV replication, suggesting that other HIV-1 specific CD8.sup.+ effector T cell subsets may be key players in HIV control. Stem cell-like memory T cells (T.sub.SCM) are a subset of T cells with a long half-life and self-renewal capacity. They serve as key reservoirs for HIV and contribute a significant barrier to HIV eradication. The present study evaluated vaccine-induced antiviral responses and T.sub.SCM cells in volunteers vaccinated with a subtype C prophylactic HIV-1 vaccine candidate administered in a prime-boost regimen. We found that ADVAX DNA prime followed by MVA boost induced significantly more peripheral CD8.sup.+ T.sub.SCM cells and higher levels of CD8.sup.+ T cell-mediated inhibition of replication of different HIV-1 clades as compared to MVA alone and placebo. These findings are novel and provide encouraging evidence to demonstrate the induction of T.sub.SCM and cytotoxic immune responses by a subtype C HIV-1 prophylactic vaccine administered using a prime-boost strategy.