Browsing by Author "Kiwanuka, Noah"
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- ItemImmune activation alters cellular and humoral responses to yellow fever 17D vaccine(The Journal of Clinical Investigation, 2014-07) Muyanja, Enoch; Ssemaganda, Aloysius; Ngauv, Pearline; Cubas, Rafael; Perrin, Helene; Srinivasan, Divya; Canderan, Glenda; Lawson, Benton; Kopycinski, Jakub; Graham, Amanda S.; Rowe, Dawne K.; Smith, Michaela J.; Isern, Sharon; Michael, Scott; Silvestri, Guido; Vanderford, Thomas H.; Castro, Erika; Pantaleo, Giuseppe; Singer, Joel; Gillmour, Jill; Kiwanuka, Noah; Nanvubya, Annet; Schmidt, Claudia; Birungi, Josephine; Cox, Josephine; Haddad, Elias K.; Kaleebu, Pontiano; Fast, Patricia; Sekaly, Rafick-Pierre; Trautmann, LydieBackground. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. Results. We showed that YF-17D–induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D–neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Trial registration. Registration is not required for observational studies. Funding. This study was funded by Canada’s Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.
- ItemPhylogenetic Networks and Parameters Inferred from HIV Nucleotide Sequences of High-Risk and General Population Groups in Uganda: Implications for Epidemic Control(Viruses, 2021) Kitayimbwa, John M.; Bbosa, Nicholas; Ssemwanga, Deogratius; Nsubuga, Rebecca N.; Kiwanuka, Noah; Bagaya, Bernard S.; Ssekagiri, Alfred; Gonzalo, Yebra; Kaleebu, Pontiano; Leigh-Brown, AndrewPhylogenetic inference is useful in characterising HIV transmission networks and assessing where prevention is likely to have the greatest impact. However, estimating parameters that influence the network structure is still scarce, but important in evaluating determinants of HIV spread. We analyzed 2017 HIV pol sequences (728 Lake Victoria fisherfolk communities (FFCs), 592 female sex workers (FSWs) and 697 general population (GP)) to identify transmission networks on Maximum Likelihood (ML) phylogenetic trees and refined them using time-resolved phylogenies. Network generative models were fitted to the observed degree distributions and network parameters, and corrected Akaike Information Criteria and Bayesian Information Criteria values were estimated. 347 (17.2%) HIV sequences were linked on ML trees (maximum genetic distance _4.5%, _95% bootstrap support) and, of these, 303 (86.7%) that consisted of pure A1 (n = 168) and D (n = 135) subtypes were analyzed in BEAST v1.8.4. The majority of networks (at least 40%) were found at a time depth of _5 years. The waring and yule models fitted best networks of FFCs and FSWs respectively while the negative binomial model fitted best networks in the GP. The network structure in the HIV-hyperendemic FFCs is likely to be scale-free and shaped by preferential attachment, in contrast to the GP. The findings support the targeting of interventions for FFCs in a timely manner for effective epidemic control. Interventions ought to be tailored according to the dynamics of the HIV epidemic in the target population and understanding the network structure is critical in ensuring the success of HIV prevention programs.
- ItemRepeat Voluntary HIV Counseling and Testing (VCT), Sexual Risk Behavior and HIV Incidence in Rakai, Uganda(Springer Science+Business Media, LLC, 2006) Matovu, Joseph K. B.; Gray, Ronald H.; Kiwanuka, Noah; Kigozi, Godfrey; Wabwire-Mangen, Fred; Nalugoda, Fred; Serwadda, David; Sewankambo, Nelson K.; Wawer, Maria J.We examined the effects of repeat Voluntary HIV counseling and testing (VCT) on sexual risk behaviors and HIV incidence in 6,377 initially HIV-negative subjects enrolled in a prospective STD control for HIV prevention trial in rural Rakai district, southwestern Uganda. Sixty-four percent accepted VCT, and of these, 62.2% were first time acceptors while 37.8% were repeat acceptors. Consistent condom use was 5.8% in repeat acceptors, 6.1% in first time acceptors and 5.1% in non-acceptors. A higher proportion of repeat acceptors (15.9%) reported inconsistent condom use compared to first-time acceptors (12%) and non-acceptors (11.7%). Also, a higher proportion of repeat acceptors (18.1%) reported 2+ sexual partners compared to first-time acceptors (14.1%) and non-acceptors (15%). HIV incidence rates were 1.4/100 py (person-years) in repeat acceptors, 1.6/100 py in first time acceptors and 1.6/100 py in non-acceptors. These data suggest a need for intensive risk-reduction counseling interventions targeting HIV-negative repeat VCT acceptors as a special risk group.