Dr. Mangala Rao received her Ph.D. in Biochemistry from The Indian Institute of Science, Bangalore, India. She completed her postdoctoral fellowship on IgE receptors on B lymphocytes in the laboratories of Dr. Arnold Froese, University of Manitoba, Canada, and Dr. Daniel H. Conrad, Johns Hopkins University School of Medicine, Baltimore, MD. She joined Dr. Carl R. Alving in 1990 as an NRC Senior Research Associate in the Department of Membrane Biochemistry, Division of Biochemistry at the Walter Reed Army Institute of Research and then became a research chemist in 1994. The department later merged with the US Military HIV Research Program.
The focus of the Rao laboratory has been to develop Army Liposome Formulations (ALF) as carriers of antigens and vaccines, develop novel delivery technologies including needle-free transcutaneous immunization (TCI), elucidate the mechanism(s) of ALF adjuvants, and conduct preclinical testing of vaccines in small animals and in nonhuman primates. These projects have utilized malaria, Ebola, dengue, anthrax, HIV, and SARS-COV-2 antigens, with a particular focus on HIV-1 antigens and V2-specific immune responses. The Rao laboratory has also been conducting mouse immunogenicity studies with SARS-COV-2 antigens formulated with ALFQ (ALF containing QS21) in support of WRAIR’s COVID-19 vaccine efforts.
In addition to elucidating the mechanism of ALF adjuvants, the Rao lab is also evaluating the effect of ALF adjuvants on HIV-1 infection in human macrophages and T cells in vitro and its effects on cell surface receptors. Surprisingly there are major gaps in our understanding of the timing and the major events that occur upon HIV-1 entry at the early time points, the types of cells and receptors involved, and the early immune responses generated. To address these questions, novel binding and functional assays such as integrin binding inhibition, virus capture, Microscale Thermophoresis (MST), surface plasmon resonance, Meso Scale Discovery electrochemiluminescence (MSD), ADCC, and ADCP assays have been developed in the lab. These assays also been utilized to evaluate preclinical and clinical samples during early infection and after vaccination with novel adjuvants and carrier systems, and to understand the role of neutralizing and non-neutralizing antibodies in preventing the early entry of HIV into cells.
Studies conducted by the Rao lab using a humanized DRAGA mouse (NOD.Rag1KO.IL2RγcKO mice expressing HLA-DR0401 and HLA A2 molecules) generated by the Navy malaria group, demonstrated this mouse to be a good model for studying HIV infection and pathogenesis. In this humanized mouse model, T follicular helper cells accumulate in the gut and female reproductive tract and are highly permissive to HIV. The functional role of TFH cells in HIV-1 infection, evaluation of the efficacy of HIV-1 candidate vaccines, and the suitability of humanized DRAGA mice as a model for HIV-1 cure are some of the research projects being pursued by the Rao laboratory.
Rao M, Peachman KK, Alving CR. Liposome Formulations as Adjuvants for Vaccines. Curr Top Microbiol Immunol. 2020 Nov 10. doi: 10.1007/82_2020_227. Online ahead of print.PMID: 33165871.
Om K, Paquin-Proulx D, Montero M, Peachman K, Shen X, Wieczorek L, Beck Z, Weiner JA, Kim D, Li Y, Mdluli T, Shubin Z, Bryant C, Sharma V, Tokarev A, Dawson P, White Y, Appelbe O, Klatt NR, Tovanabutra S, Estes JD, Matyas GR, Ferrari G, Alving CR, Tomaras GD, Ackerman ME, Michael NL, Robb ML, Polonis V, Rolland M, Eller MA, Rao M, Bolton DL. Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge. PLoS Pathog. 2020 Sep 3;16(9):e1008764. doi: 10.1371/journal.ppat.1008764. eCollection 2020 Sep.
Wieczorek L, Peachman K, Adams DJ, Barrows B, Molnar S, Schoen J, Dawson P, Bryant C, Chenine AL, Sanders-Buell E, Srithanaviboonchai K, Pathipvanich P, Michael NL, Robb ML, Tovanabutra S, Rao M, Polonis VR. Evaluation of HIV-1 neutralizing and binding antibodies in maternal-infant transmission in Thailand. Virology. 2020 Sep;548:152-159. doi: 10.1016/j.virol.2020.05.007. Epub 2020 Jun 24.PMID: 32838936
Alving CR, Peachman KK, Matyas GR, Rao M, Beck Z. Army Liposome Formulation (ALF) family of vaccine adjuvants. Expert Rev Vaccines. 2020 Mar;19(3):279-292. doi: 10.1080/14760584.2020.1745636. Epub 2020 Mar 31. PubMed PMID: 32228108; PubMed Central PMCID: PMC7412170.
Easterhoff D, Pollara J, Luo K, Janus B, Gohain N, Williams LD, Tay MZ, Monroe A, Peachman K, Choe M, Min S, Lusso P, Zhang P, Go EP, Desaire H, Bonsignori M, Hwang KK, Beck C, Kakalis M, O'Connell RJ, Vasan S, Kim JH, Michael NL, Excler JL, Robb ML, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Nitayaphan S, Sinangil F, Tartaglia J, Phogat S, Wiehe K, Saunders KO, Montefiori DC, Tomaras GD, Moody MA, Arthos J, Rao M, Joyce MG, Ofek G, Ferrari G, Haynes BF. HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions. JCI Insight. 2020 Jan 30;5(2). doi: 10.1172/jci.insight.131437. PubMed PMID: 31996483; PubMed Central PMCID: PMC7098725.
Trinh HV, Gohain N, Pham PT, Hamlin C, Song H, Sanders-Buell E, Bose M, Eller LA, Jain S, Uritskiy G, Rao VB, Tovanabutra S, Michael NL, Robb ML, Joyce MG, Rao M. Humoral Response to the HIV-1 Envelope V2 Region in a Thai Early Acute Infection Cohort. Cells. 2019 Apr 19;8(4). doi: 10.3390/cells8040365. PubMed PMID: 31010245; PubMed Central PMCID: PMC6523213.
Rao M, Onkar S, Peachman KK, White Y, Trinh HV, Jobe O, Zhou Y, Dawson P, Eller MA, Matyas GR, Alving CR. Liposome-Encapsulated Human Immunodeficiency Virus-1 gp120 Induces Potent V1V2-Specific Antibodies in Humans. J Infect Dis. 2018 Oct 5;218(10):1541-1550. doi: 10.1093/infdis/jiy348. PubMed PMID: 29893872.
Wen Y, Trinh HV, Linton CE, Tani C, Norais N, Martinez-Guzman D, Ramesh P, Sun Y, Situ F, Karaca-Griffin S, Hamlin C, Onkar S, Tian S, Hilt S, Malyala P, Lodaya R, Li N, Otten G, Palladino G, Friedrich K, Aggarwal Y, LaBranche C, Duffy R, Shen X, Tomaras GD, Montefiori DC, Fulp W, Gottardo R, Burke B, Ulmer JB, Zolla-Pazner S, Liao HX, Haynes BF, Michael NL, Kim JH, Rao M, O'Connell RJ, Carfi A, Barnett SW. Generation and characterization of a bivalent protein boost for future clinical trials: HIV-1 subtypes CR01_AE and B gp120 antigens with a potent adjuvant. PLoS One. 2018;13(4):e0194266. doi: 10.1371/journal.pone.0194266. eCollection 2018. PubMed PMID: 29698406; PubMed Central PMCID: PMC5919662.
Kim J, Peachman KK, Jobe O, Morrison EB, Allam A, Jagodzinski L, Casares SA, Rao M. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model. Front Immunol. 2017;8:1405. doi: 10.3389/fimmu.2017.01405. eCollection 2017. PubMed PMID: 29163484; PubMed Central PMCID: PMC5663722.
Jobe O, Trinh HV, Kim J, Alsalmi W, Tovanabutra S, Ehrenberg PK, Peachman KK, Gao G, Thomas R, Kim JH, Michael NL, Alving CR, Rao VB, Rao M. Effect of cytokines on Siglec-1 and HIV-1 entry in monocyte-derived macrophages: the importance of HIV-1 envelope V1V2 region. J Leukoc Biol. 2016 Jun;99(6):1089-106. doi: 10.1189/jlb.2A0815-361R. Epub 2015 Dec 14. PubMed PMID: 26667473; PubMed Central PMCID: PMC4952014.
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