Weerasuriya CK, Harris RC, McQuaid CF, Bozzani F, Ruan Y, Li R, Li T, Rade K, Rao R, Ginsberg AM, Gomez GB, White RGThe epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China. BMC Med 2021;19(1):60 doi: 10.1186/s12916-021-01932-7
Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India.
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Kitandwe PK, Muyanja E, Nakaweesa T, Nanvubya A, Ssetaala A, Mpendo J, Okech B, Bagaya BS, Kiwanuka N, Price MAHepatitis B prevalence and incidence in the fishing communities of Lake Victoria, Uganda: a retrospective cohort study. BMC Public Health 2021;21(1):394 doi: 10.1186/s12889-021-10428-1
Hepatitis B is a serious potentially fatal hepatocellular disease caused by the hepatitis B virus. In the fishing communities of Lake Victoria Uganda, the hepatitis B virus infection burden is largely unknown. This study assessed the prevalence and incidence of hepatitis B in these communities.
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Hassan AS, Hare J, Gounder K, Nazziwa J, Karlson S, Olsson L, Streatfield C, Kamali A, Karita E, Kilembe W, Price MA, Borrow P, Björkman P, Kaleebu P, Allen S, Hunter E, Ndung'u T, Gilmour J, Rowland-Jones S, Esbjörnsson J, Sanders EJA Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome. Clin Infect Dis 2021; doi: ciab139
Acute retroviral syndrome (ARS) is associated with HIV-1 subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS.
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Wall KM, Karita E, Nyombayire J, Ingabire R, Mukamuyango J, Parker R, Brill I, Price M, Haddad LB, Tichacek A, Hunter E, Allen SGenital abnormalities, hormonal contraception, and HIV transmission risk in Rwandan serodifferent couples. J Infect Dis 2021; doi: jiab071
We explored the role of genital abnormalities and hormonal contraception in HIV transmission among heterosexual serodifferent couples in Rwanda.
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Charles TP, Burton SL, Arunachalam PS, Cottrell CA, Sewall LM, Bollimpelli VS, Gangadhara S, Dey AK, Ward AB, Shaw GM, Hunter E, Amara RR, Pulendran B, van Gils MJ, Derdeyn CAThe C3/465 glycan hole cluster in BG505 HIV-1 envelope is the major neutralizing target involved in preventing mucosal SHIV infection. PLoS Pathog 2021;17(2):e1009257 doi: 10.1371/journal.ppat.1009257
Stabilized HIV-1 envelope (Env) trimers elicit tier 2 autologous neutralizing antibody (nAb) responses in immunized animals. We previously demonstrated that BG505 SOSIP.664.T332N gp140 (BG505 SOSIP) immunization of rhesus macaques (RM) provided robust protection against autologous intra-vaginal simian-human immunodeficiency virus (SHIV) challenge that was predicted by high serum nAb titers. Here, we show that nAb in these protected RM targeted a glycan hole proximal to residue 465 in gp120 in all cases. nAb also targeted another glycan hole at residues 241/289 and an epitope in V1 at varying frequencies. Non-neutralizing antibodies directed at N611-shielded epitopes in gp41 were also present but were more prevalent in RM with low nAb titers. Longitudinal analysis demonstrated that nAb broadened in some RM during sequential immunization but remained focused in others, the latter being associated with increases in nAb titer. Thirty-eight monoclonal antibodies (mAbs) isolated from a protected RM with an exceptionally high serum neutralization titer bound to the trimer in ELISA, and four of the mAbs potently neutralized the BG505 Env pseudovirus (PV) and SHIV. The four neutralizing mAbs were clonally related and targeted the 465 glycan hole to varying degrees, mimicking the serum. The data demonstrate that the C3/465 glycan hole cluster was the dominant neutralization target in high titer protected RM, despite other co-circulating neutralizing and non-neutralizing specificities. The isolation of a neutralizing mAb family argues that clonotype expansion occurred during BG505 SOSIP immunization, leading to high titer, protective nAb and setting a desirable benchmark for HIV vaccines.
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Osier FHA, Murungi LMSmashing Stereotypes: Mutual Respect, Key to Embracing Diversity. Trends Parasitol 2021; doi: S1471-4922(21)00007-6
The path to a successful international career in science is daunting for most, and women in Africa are no exception. We are grossly under-represented as senior authors in high-impact publications and keynote speakers at international conferences, and rarely head major funding networks. Smashing long-held stereotypes may ease the journey.
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Nanyonjo G, Asiki G, Ssetaala A, Nakaweesa T, Wambuzi M, Nanvubya A, Mpendo J, Okech B, Kitandwe PK, Nielsen L, Nalutaaya A, Welsh S, Bagaya BS, Chinyenze K, Fast P, Price M, Kiwanuka NPrevalence and correlates of HIV infection among adolescents and young people living in fishing populations along Lake Victoria Fishing Communities in Uganda. Pan Afr Med J 2020;37:208 doi: 10.11604/pamj.2020.37.208.26124
fishing communities in Uganda are key populations for HIV, with persistently higher prevalence and incidence than the general population.
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Bruxelle JF, Trattnig N, Mureithi MW, Landais E, Pantophlet RHIV-1 Entry and Prospects for Protecting against Infection. Microorganisms 2021;9(2) doi: 228
Human Immunodeficiency Virus type-1 (HIV-1) establishes a latent viral reservoir soon after infection, which poses a major challenge for drug treatment and curative strategies. Many efforts are therefore focused on blocking infection. To this end, both viral and host factors relevant to the onset of infection need to be considered. Given that HIV-1 is most often transmitted mucosally, strategies designed to protect against infection need to be effective at mucosal portals of entry. These strategies need to contend also with cell-free and cell-associated transmitted/founder (T/F) virus forms; both can initiate and establish infection. This review will discuss how insight from the current model of HIV-1 mucosal transmission and cell entry has highlighted challenges in developing effective strategies to prevent infection. First, we examine key viral and host factors that play a role in transmission and infection. We then discuss preventive strategies based on antibody-mediated protection, with emphasis on targeting T/F viruses and mucosal immunity. Lastly, we review treatment strategies targeting viral entry, with focus on the most clinically advanced entry inhibitors.
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Kapaata A, Balinda SN, Xu R, Salazar MG, Herard K, Brooks K, Laban K, Hare J, Dilernia D, Kamali A, Ruzagira E, Mukasa F, Gilmour J, Salazar-Gonzalez JF, Yue L, Cotten M, Hunter E, Kaleebu PHIV-1 Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity. Viruses 2021;13(2) doi: 171
The ability to efficiently establish a new infection is a critical property for human immunodeficiency virus type 1 (HIV-1). Although the envelope protein of the virus plays an essential role in receptor binding and internalization of the infecting virus, the structural proteins, the polymerase and the assembly of new virions may also play a role in establishing and spreading viral infection in a new host. We examined Ugandan viruses from newly infected patients and focused on the contribution of the genes to replication capacity. A panel of sequences generated using single genome amplification from incident HIV-1 infections were cloned into a common HIV-1 NL4.3 pol/env backbone and the influence of changes on replication capacity was monitored. Using a novel protein domain approach, we then documented diversity in the functional protein domains across the region and identified differences in the Gag-p6 domain that were frequently associated with higher in vitro replication.
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Crowell TA, Fast PE, Bekker LG, Sanders EJResponse to: 'Inclusion as Illusion: Erasing Transgender Women in Research with MSM'. J Int AIDS Soc 2021;24(1):e25662 doi: 10.1002/jia2.25662
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