Tuberculosis (TB) is the most common cause of death in people living with HIV. BCG delivered intradermally (ID) is the only licensed vaccine to prevent TB. However, it offers little protection from pulmonary TB in adults. Intravenous (IV) BCG, but not ID BCG, confers striking protection against (Mtb) infection and disease in rhesus macaques. We investigated whether IV BCG could protect against TB in macaques with a pre-existing SIV infection. There was a robust influx of airway T cells following IV BCG in both SIV-infected and SIV-naïve animals, with elevated antibody titers in plasma and airways. Following Mtb challenge, all 7 SIV-naïve and 9 out of 12 SIV-infected vaccinated animals were completely protected, without any culturable bacilli in their tissues. PBMC responses post-challenge indicated early clearance of Mtb in vaccinated animals regardless of SIV infection. These data support that IV BCG is immunogenic and efficacious in SIV-infected animals.
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http://dx.doi.org/10.21203/rs.3.rs-2802306/v1 | DOI Listing |
PLoS Pathog
January 2025
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
The latent viral reservoir remains the major barrier to HIV cure, placing the burden of strict adherence to antiretroviral therapy (ART) on people living with HIV to prevent recrudescence of viremia. For infants with perinatally acquired HIV, adherence is anticipated to be a lifelong need. In this study, we tested the hypothesis that administration of ART and viral Envelope-specific rhesus-derived IgG1 monoclonal antibodies (RhmAbs) with or without the IL-15 superagonist N-803 early in infection would limit viral reservoir establishment in SIV-infected infant rhesus macaques.
View Article and Find Full Text PDFCell Rep
January 2025
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques.
View Article and Find Full Text PDFPurpose Of Review: Women are underrepresented in HIV infection and prevention research despite making up half of people living with HIV. The female genital tract (FGT) serves as a primary site of HIV acquisition, but gaps in knowledge remain regarding protective innate immune mechanisms. Innate lymphoid cells are tissue-resident cells involved in mucosal barrier maintenance and protection, and innate lymphoid cells (ILCs) are altered during chronic HIV infection.
View Article and Find Full Text PDFCurr Opin HIV AIDS
December 2024
Department of Infectious Diseases and Microbiology, Graduate School of Public Health.
Purpose Of Review: Typically, both HIV-infected humans and simian immunodeficiency virus (SIV)-infected Asian nonhuman primates (NHPs) eventually progress to AIDS, while African NHPs that are natural hosts of SIV do not, in spite of life-long, high levels of viral replication. Lack of disease progression in African NHPs is not due to some adaptation by the virus, but rather to host adaptations to the virus. Central to these adaptations is maintenance of the gut integrity during acute viral replication and inflammation, which allows natural hosts to avoid the chronic inflammation characteristic to pathogenic HIV/SIV infection.
View Article and Find Full Text PDFCurr Opin HIV AIDS
December 2024
Division of Innate and Comparative Immunology, Center for Human Systems Immunology, Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Purpose Of Review: Like elephants (and T cells), accumulating evidence suggest natural killer (NK) cells never forget. The description of adaptive or memory NK cells, which can be induced by HIV/SIV infections and vaccines and associated with protective effects in persons with HIV (PWH), has dramatically increased the interest in leveraging NK cells to prevent HIV infection or suppress HIV reservoirs. However, harnessing their full antiviral potential has been hindered by an incomplete understanding of mechanisms underlying adaptive NK cell development and infected cell recognition.
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