Superior Control of HIV-1 Replication by CD8+ T Cells Targeting Conserved Epitopes: Implications for HIV Vaccine Design. e64405

• Published in: PloS one 2013-05, Vol.8 (5)
• Main Authors: Kunwar, Pratima, Hawkins, Natalie, Dinges, Warren L, Liu, Yi, Gabriel, Erin E, Swan, David A, Stevens, Claire E, Maenza, Janine, Collier, Ann C, Mullins, James I
• Format: Article
• Language: English
• Subjects: Human immunodeficiency virus 1
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0064405

A successful HIV vaccine will likely induce both humoral and cell-mediated immunity, however, the enormous diversity of HIV has hampered the development of a vaccine that effectively elicits both arms of the adaptive immune response. To tackle the problem of viral diversity, T cell-based vaccine approaches have focused on two main strategies (i) increasing the breadth of vaccine-induced responses or (ii) increasing vaccine-induced responses targeting only conserved regions of the virus. The relative extent to which set-point viremia is impacted by epitope-conservation of CD8+ T cell responses elicited during early HIV-infection is unknown but has important implications for vaccine design. To address this question, we comprehensively mapped HIV-1 CD8+ T cell epitope-specificities in 23 ART-naive individuals during early infection and computed their conservation score (CS) by three different methods (prevalence, entropy and conseq) on clade-B and group-M sequence alignments. The majority of CD8+ T cell responses were directed against variable epitopes (p