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Probiotic Therapy During Vaccination Alters Antibody Response to Simian-Human Immunodeficiency Virus Infection But Not to Commensals
Wilson et al., AIDS Research and Human Retroviruses. 2023.
https://www.doi.org/10.1089/AID.2022.0123
Strategies to boost vaccine-induced mucosal humoral responses are critical to developing an HIV-1 vaccine, and probiotic supplementation could help boost antibody responses. Researchers analyzed antibody titers to explore this topic in rhesus macaques (sex not specified) infected with simian–human immunodeficiency virus (SHIV). They reported that probiotic treatment during vaccination led to delayed kinetics in the circulating HIV-specific IgA response after breakthrough SHIV infection. These findings highlight the potential of probiotic supplementation for reducing IgA-specific HIV antibodies in the plasma, which could help reduce HIV acquisition in vaccinated individuals. Supported by ORIP (P51OD011104, R21OD031435) and NIAID.
Cannabinoid Enhancement of lncRNA MMP25-AS1/MMP25 Interaction Reduces Neutrophil Infiltration and Intestinal Epithelial Injury in HIV/SIV Infection
Premadasa et al., Journal of Clinical Investigation Insight. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132162/
Gastrointestinal CD4+ T cell depletion during acute simian immunodeficiency virus (SIV) and HIV infection causes significant structural and functional damage, disrupting intestinal immune homeostasis and leading to intestinal epithelial barrier dysfunction. Oral phytocannabinoids are safe and well tolerated in people with HIV, but more information is needed regarding the effects of long-term tetrahydrocannabinol (THC) use on the intestinal epithelial compartment. Investigators profiled gene expression in the colonic epithelium of SIV-infected rhesus macaques of both sexes that were administered THC. They reported that low-dose THC can reduce neutrophil infiltration and intestinal epithelial injury, potentially by downregulating MMP25 expression through modulation of a long noncoding RNA, MMP25-AS1. Supported by ORIP (P51OD011104, P51OD011103), NIAID, and NIDA.
Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or β-Sheet Conformations on Time of SIVmac251 Acquisition
Stamos et al., Journal of Virology. 2023.
https://journals.asm.org/doi/10.1128/jvi.01864-22
Research suggests that the SIV variable region 2 (V2) is a region of virus vulnerability, likely because of its exposure on the apex of virions and on the surfaces of SIV-infected cells. Researchers examined the effects of two monoclonal antibodies, NCI05 and NCI09, on the acquisition of SIV using rhesus macaques (sex not specified). They found that NCI05, but not NCI09, delays SIV acquisition, highlighting the complexity of antibody responses to V2. Both antibodies were unable to decrease the risk of viral acquisition. This study demonstrates that such antibodies as NCI05 alone are insufficient to protect against SIV acquisition. Supported by ORIP (S10OD027000), NIAID, and NCI.
Longitudinal Characterization of Circulating Extracellular Vesicles and Small RNA During Simian Immunodeficiency Virus Infection and Antiretroviral Therapy
Huang et al., AIDS. 2023.
https://www.doi.org/10.1097/QAD.0000000000003487
Antiretroviral therapy is effective for controlling HIV infection but does not fully prevent early aging disorders or serious non-AIDS events among people with HIV. Using pigtail and rhesus macaques (sex not specified), researchers profiled extracellular vesicle small RNAs during different phases of simian immunodeficiency virus infection to explore the potential relationship between extracellular vesicle–associated small RNAs and the infection process. They reported that average particle counts correlated with infection, but the trend could not be explained fully by virions. These findings raise new questions about the distribution of extracellular vesicle RNAs in HIV latent infection. Supported by ORIP (U42OD013117), NIDA, NIMH, NIAID, NCI, and NINDS.
Infant Rhesus Macaques Immunized Against SARS-CoV-2 Are Protected Against Heterologous Virus Challenge 1 Year Later
Milligan et al., Science Translational Medicine. 2023.
https://doi.org/10.1126/scitranslmed.add6383
The Moderna and Pfizer–BioNTech mRNA vaccines received emergency use authorization for infants 6 months and older in June 2022, but questions remain regarding the durability of vaccine efficacy against emerging variants in this age group. Using a two-dose vaccine regimen consisting of stabilized prefusion Washington-strain spike protein encoded by mRNA and encapsulated in lipid nanoparticles, the investigators immunized 2-month-old rhesus macaques of both sexes. They found that the immune responses persisted and protected from severe disease after heterologous challenge with the Delta variant 1 year later. The decay kinetics of vaccine-induced neutralizing antibody responses in the infant monkeys are comparable to those observed in adult humans and nonhuman primates. Supported by ORIP (P51OD011107), NIAID, and NCI.
A Live Dengue Virus Vaccine Carrying a Chimeric Envelope Glycoprotein Elicits Dual DENV2–DENV4 Serotype-Specific Immunity
Young et al., Nature Communications. 2023.
https://pubmed.ncbi.nlm.nih.gov/36914616/
Dengue vaccine development is challenging because some virus-specific antibodies are protective, whereas others are implicated in enhanced viral replication and more severe disease. Current dengue tetravalent vaccines contain four live attenuated serotypes formulated to induce balanced protective immunity. To simplify live-virus vaccine design, investigators identified co-evolutionary constraints inherent in flavivirus virion assembly. They found that the chimeric virus replicated efficiently in vitro and in vivo and that a single inoculation induced type-specific neutralizing antibodies in male macaques. These findings can be applied to the development of bivalent live dengue vaccines that induce independent immunity to multiple serotypes. Supported by ORIP (P40OD012217) and NIAID.
Late Gene Expression–Deficient Cytomegalovirus Vectors Elicit Conventional T Cells That Do Not Protect Against SIV
Hansen et al., Journal of Clinical Investigation Insight. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070102/
Cytomegalovirus (CMV)–based vaccines aim to exploit unique immunological adaptations, including host manipulation and immune evasion strategies. Translating CMV-based vaccines from rhesus macaques to humans requires translating the immune factors responsible for efficacy, as well as vaccine vectors that are sufficiently safe for widespread use. Researchers examined the impact of a stringent attenuation strategy on vector-induced immune protection against simian immunodeficiency virus (SIV) in rhesus macaques of both sexes. They reported that elicited CD8+ T cells exclusively failed to protect against SIV challenge. These data suggest that late viral gene expression and/or residual in vivo spreading are required to induce protective CD8+ T cell responses. Supported by ORIP (P51OD011092, P51OD011107, S10OD016261), NCI, NIAID, and NCATS.
Chronic Immune Activation and Gut Barrier Dysfunction Is Associated with Neuroinflammation in ART-Suppressed SIV+ Rhesus Macaques
Byrnes et al., PLOS Pathogens. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10085024/
About 40% of people with HIV develop neurocognitive disorders, potentially resulting from persistent infection in the brain and neuroinflammation. Investigators characterized the central nervous system reservoir and immune environment of simian immunodeficiency virus (SIV)–infected rhesus macaques of both sexes during acute, chronic, or antiretroviral therapy (ART)–suppressed infection. They reported that neuroinflammation and blood–brain barrier dysfunction correlated with viremia and immune activation in the gut. Their findings suggest that gastrointestinal tract damage can contribute to neuroimmune activation and inflammation, even in the absence of SIV or HIV infection. This work also has implications for other neurological disorders where chronic inflammation is associated with pathogenesis. Supported by ORIP (P51OD011132, P51OD011092, U42OD011023, R24OD010445), NIAID, NCI, and NIMH.
Cannabinoids Modulate the Microbiota–Gut–Brain Axis in HIV/SIV Infection by Reducing Neuroinflammation and Dysbiosis while Concurrently Elevating Endocannabinoid and Indole-3-Propionate Levels
McDew-White et al., Journal of Neuroinflammation. 2023.
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02729-6
Chronic neuroinflammation is thought to be a significant contributor to HIV-associated neurocognitive disorders. Using rhesus macaques of both sexes, researchers investigated the effects of simian immunodeficiency virus (SIV) infection on the microbiota–gut–brain axis (MGBA), as well as the use of low-dose cannabinoids to reverse MGBA dysregulation. They reported that tetrahydrocannabinol reduced neuroinflammation and dysbiosis and increased plasma endocannabinoid, endocannabinoid-like, glycerophospholipid, and indole-3-propionate levels. This study offers a potential strategy to promote brain health in people with HIV. Supported by ORIP (P51OD011104, P51OD011103), NIAID, and NIDA.
Assessment of Anti-CD20 Antibody Pre-Treatment for Augmentation of CAR-T Cell Therapy in SIV-Infected Rhesus Macaques
Pampusch et al., Frontiers in Immunology. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9941136/
Chronic HIV replication occurs primarily within lymphoid follicles, and investigators hypothesized that temporary disruption of these follicles would create space for chimeric antigen receptor (CAR) T cell engraftment and lead to increased abundance and persistence of CAR T cells. They evaluated CAR T cell abundance and persistence in rhesus macaques of both sexes following simian immunodeficiency virus (SIV) infection and antiretroviral therapy suppression. Their results suggest that CAR T cells expanded to a greater extent in the depleted and CAR T cell–treated animals. Further studies are needed to evaluate strategies for engraftment and the persistence of HIV-specific CAR T cells. Supported by ORIP (P51OD011106, P51RR000167), NIAID, and NIDA.