Browsing by Author "Mugaba, S."
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Item Group M consensus Gag and Nef peptides are as efficient at detecting clade A1 and D cross-subtype T-cell functions as subtype-specific consensus peptides(Vaccine, 2014) Mugaba, S.; Nakiboneka, R.; Nanyonjo, M.; Bugembe-Lule, D.; Kaddu, I.; Nanteza, B.; Tweyongyere, R.; Kaleebu, P.; Serwanga, J.Evaluating HIV-1 specific T-cell response in African populations is sometimes compromised by extensive virus diversity and paucity of non-clade B reagents. We evaluated whether consensus group M (ConM) peptides could serve as comparable substitutes for detecting immune responses in clade A and clade D HIV-1 infection. Frequencies, breadths and polyfunctionality (≥3 functions: IFN-γ, IL-2, TNF-α and Perforin) of HIV-specific responses utilizing ConM, ConA and ConD Gag and Nef peptides was compared. Median genetic distances of infecting gag sequences from consensus group M were (8.9%, IQR 8.2–9.7 and 9%, IQR 3.3–10) for consensus A and D, respectively. Of 24 subjects infected with A and D clade virus, Gag responses were detected in comparable proportions of subjects when using ConM peptides 22/24, ConA peptides 17/24, and ConD peptides 21/24; p=0.12. Nef responses were also detected at similar proportions of subjects when using ConM peptides 15/23, ConA peptides 19/23, and ConD peptides 16/23, p=0.39. Virus-specific CD4+ and CD8+ T-cell polyfunctionality were also detected in similar proportions of infected individuals when using different peptide sets. These data support the use of consensus group M overlapping peptide sets as reagents for detecting HIV-specific responses in a clade A and D infected population, but underscore the limitations of utilizing these reagents when evaluating the breadth of virus-specific responses.Item P16-03. Persistence of robust cross-reactive group M consensus T-cell responses in a chronic HIV-1 clade A1 and D-infected Ugandan population(Retrovirology, 2009) Serwanga, J.J.; Mugaba, S.; Pimego, E.E.; Lyagoba, F.F.; Nanteza, B.B.; Katongole, E.M.; Ndembi, N.N.; Kaleebu, P.P.HIV-1 group-M exhibits extraordinary genetic variation, cross-reactivity of immunogens based on consensus clades could be continuously diminishing as the AIDS epidemic progresses. Characterisation of cross-reactive T-cell responses to more central group M consensus peptides in this multi-clade population has not been performed; and could be pertinent for global vaccineItem P20-10. Differences in patterns of Gag-induced immunogenetic pressure occur between clades A and D chronic HIV-1 infection in a Ugandan population(Retrovirology, 2009) Serwanga, J.; Ndembi, N.; Nanteza, B.; Mugaba, S.; Pimego, E.; Pala, P.; Auma, B.; Lyagoba, F.; Kaleebu, P.We previously reported slow HIV-1 disease progression in this population to be associated with the inherent host HLA B allele-mediated ability to induce broader Gag T-cell responses and faster disease progression to be more associated with clade D than A. Since Gag escape mutations often reduce viral fitness leading to significant reduction in virus replication, in this study, we evaluated the immunogenetic characteristics of clades A and D-associated escape mutations that could be harnessed for vaccine design.