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Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (TsubRM/sub) CD8sup+/supT-cells is of great interest, but limited data exist on TsubRM/sub-like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8sup+/supT-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and a transcriptionally TsubRM/sub-like profile distinct from blood CD8sup+/supT-cells. In PLWH, CD8sup+/supTsubRM/sub-like cells are expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8sup+/supT-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8sup+/supT-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIV-specific CD8sup+/supTsubRM/sub-like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs.

The economic and humanistic impact of COVID-19 pandemic is enormous globally. No definitive treatment exists, hence accelerated development and approval of COVID-19 vaccines, offers a unique opportunity for COVID-19 prevention and control. Vaccine hesitancy may limit the success of vaccine distribution in Africa, therefore we assessed the potentials for coronavirus vaccine hesitancy and its determinants among Africans. An online cross-sectional African-wide survey was administered in Arabic, English, and French languages. Questions on demographics, self-reported health status, vaccine literacy, knowledge and perception on vaccines, past experience, behavior, infection risk, willingness to receive and affordability of the SARS-COV-2 vaccine were asked. Data were subjected to descriptive and inferential statistics. A total of 5,416 individuals completed the survey. Approximately, 94% were residents of 34 African countries while the other Africans live in the Diaspora. Only 63% of all participants surveyed were willing to receive the COVID-19 vaccination as soon as possible and 79% were worried about its side effects. Thirty-nine percent expressed concerns of vaccine-associated infection. The odds of vaccine hesitancy was 0.28 (95% CI: 0.22, 0.30) among those who believed their risk of infection was very high, compared to those who believed otherwise. The odds of vaccine hesitancy was one-fifth (OR = 0.21, 95% CI: 0.16, 0.28) among those who believed their risk of falling sick was very high, compared to those who believed their risk of falling very sick was very low. The OR of vaccine hesitancy was 2.72 (95% CI: 2.24, 3.31) among those who have previously refused a vaccine for themselves or their child compared to counterparts with no self-reported history of vaccine hesitancy. Participants want the vaccines to be mandatory (40%), provided free of charge (78%) and distributed in homes and offices (44%). COVID-19 vaccine hesitancy is substantial among Africans based on perceived risk of coronavirus infection and past experiences. Publisher PDF

Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue resident memory ( TRM) CD8+ T-cells is of great interest, but limited data exist on TRMs within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and transcriptionally TRM-like profile that is distinct from blood. In PLWH, CD8+ TRM-like cells are highly expanded and adopt a more cytolytic, activated and exhausted phenotype characterized by increased expression of CD69, PD-1 and perforin, but reduced CD127. This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood. Single-cell profiling of these cells revealed a clear transcriptional signature of T-cell activation, clonal expansion and exhaustion ex-vivo. In contrast, this signature was absent from HIV-specific CD8+ T-cells in tonsils isolated from a natural HIV controller, who expressed lower levels of cell surface PD-1 and CXCR5, and reduced transcriptional evidence of T-cell activation, exhaustion and cytolytic activity. Thus, we show that HIV-specific TRM-like CD8+ T-cells in tonsils from non-HIV controllers are enriched for activation and exhaustion profiles compared to those in blood, suggesting that lymphoid HIV-specific CD8+ TRM cells are potentially ideal candidates for immunotherapy to modulate their ability to targeting the HIV reservoirs.

Background: The economic and humanistic impact of the COVID-19 pandemic has been tremendous globally, including in Africa. No definitive treatment exists yet. The accelerated development and approval of COVID-19 vaccines, therefore, offers a unique opportunity for the prevention and control of COVID-19. The extent to which vaccine hesitancy may limit the success of vaccine distribution is unclear. The objective of this study was to assess the potential coronavirus vaccine hesitancy, and explore the determinants of vaccine hesitancy among Africans. Methods: An online cross-sectional continent-wide (Africa), pretested questionnaire was administered in Arabic, English, and French languages among Africans. The questionnaire comprised questions on demographics of respondents, self-reported health status and literacy, knowledge and perception of vaccines, past experience and behavior, risk assessment of SARS-COV-2, and willingness to receive, voluntariness, and affordability of the SARS-COV-2 vaccine, and vaccine education and distribution. Data obtained were subjected to descriptive and inferential statistics. Results: A total of 5,416 individuals completed the survey. Approximately, 94% were residents of 34 African countries while the others were Africans living in the Diaspora. Only 62% of participants surveyed were willing to receive the COVID-19 vaccination. A total of 79% were worried about the side effects of the vaccine, and 39% actually expressed concerns that they might get infected by receiving the vaccine. The odds ratio (OR) of vaccine hesitancy was 0.28 (95% CI: 0.22, 0.30) among those who believed their risk of infection was very high, compared to those who believed their risk of infection was very low. The OR of vaccine hesitancy was 0.21 (95% CI: 0.16, 0.28) among those who believed their risk of falling very sick was very high, compared to those who believed their risk of falling very sick was very low. The OR of vaccine hesitancy was 2.72 (95% CI: 2.24, 3.31) among those who have previously refused a vaccine for themselves or their child compared to counterparts with no self-reported history of vaccine hesitancy. Many participants want the vaccines to be made mandatory (40%), provided free of charge (78%) and distributed at homes and offices (44%). Conclusion: COVID-19 vaccine hesitancy is substantial among Africans, and this is related to perceived risk of coronavirus infection and past experiences. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: Institutional review boards from Nigeria (University of Ilorin) and Egypt (Ahram Canadian University, Faculty of Oral and Dental Medicine) approved the study.

Summary Innate lymphoid cells (ILCs) are important for response to infection and for immune development in early life. HIV infection in adults depletes circulating ILCs, but the impact on children infected from birth remains unknown. We study vertically HIV-infected children from birth to adulthood and find severe and persistent depletion of all circulating ILCs that, unlike CD4+ T cells, are not restored by long-term antiretroviral therapy unless initiated at birth. Remaining ILCs upregulate genes associated with cellular activation and metabolic perturbation. Unlike HIV-infected adults, ILCs are also profoundly depleted in tonsils of vertically infected children. Transcriptional profiling of remaining ILCs reveals ongoing cell-type-specific activity despite antiretroviral therapy. Collectively, these data suggest an important and ongoing role for ILCs in lymphoid tissue of HIV-infected children from birth, where persistent depletion and sustained transcriptional activity are likely to have long-term immune consequences that merit further investigation., Graphical Abstract, Highlights • ILCs are depleted in children born with HIV-1 infection • Only initiation of antiretroviral therapy at birth prevents ILC depletion • Blood ILCs in HIV-1 infected children upregulate activation and cellular metabolism genes • Tonsil-resident ILC3s and NK cells exhibit proliferation and innate immune signaling, ILCs are dysregulated during HIV-1 infection in adults, but their fate in children is unknown. Singh et al. demonstrate that circulating and tonsil-resident ILCs are depleted in children infected with HIV-1 since birth. Transcriptionally, ILCs exhibit cell-type- and compartment-specific activity in HIV-1 infected children compared to healthy controls.

Innate lymphoid cells (ILCs) are important for response to infection and immune development in early life. HIV infection in adults has a profound effect on ILCs, but the impact from birth is unknown. Here we studied vertically HIV infected children from birth, and found severe and persistent depletion of all circulating ILCs. In contrast to CD4 T-cells, circulating ILCs are not restored by long-term antiretroviral therapy, but could be rescued by treatment from birth. Remaining helper ILCs in blood were transcriptionally silent, whilst NK cells display limited regulation of genes associated with functional impairment, and CD4 T-cells show strong transcriptional activity. In stark contrast to blood, lymphoid (tonsil) tissue ILCs from infected children had a robust and coordinated transcriptional response to infection, while CD4 T-cell subsets were transcriptionally silent. These data suggest an important and on-going role for ILCs in lymphoid tissue of HIV infected children that requires further investigation.