Mangala Rao
A5107139162- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- HIV/AIDS drug development and treatment
- COVID-19 Clinical Research Studies
- Hepatitis B Virus Studies
- COVID-19 Impact on Reproduction
- Herpesvirus Infections and Treatments
- Glycosylation and Glycoproteins Research
- Virology and Viral Diseases
- SARS-CoV-2 detection and testing
- Bacillus and Francisella bacterial research
- Hepatitis C virus research
- Immune Response and Inflammation
- Bacteriophages and microbial interactions
- Lipid Membrane Structure and Behavior
- Immunodeficiency and Autoimmune Disorders
- Influenza Virus Research Studies
- Viral Infections and Outbreaks Research
- Blood groups and transfusion
Walter Reed Army Institute of Research
2016-2025
Purdue University West Lafayette
2024
Duke University
2024
Henry M. Jackson Foundation
2013-2020
National Cancer Institute
2020
Center for Cancer Research
2020
Catholic University of America
2011-2013
University of America
2011-2013
Fujita Health University Hospital
2013
Pitié-Salpêtrière Hospital
2013
In the RV144 trial, estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed case–control analysis to identify antibody and cellular immune correlates infection risk.
The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants concern (VoCs) and long-term threat emerging coronaviruses. Here, we design characterize four categories engineered nanoparticle immunogens that recapitulate structural antigenic properties prefusion SARS-CoV-2 spike (S), S1, receptor-binding domain (RBD). These induce robust S binding, ACE2 inhibition, authentic pseudovirus neutralizing antibodies...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (T H 1)–biased CD4 response elicited neutralizing antibodies wild type concern, as well SARS-CoV-1....
The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against gp120 envelope (Env). Peptide microarray analysis six subtypes group M consensus that vaccination induced to the second variable (V2) loop of multiple subtypes. We further evaluated V2 by ELISA surface plasmon resonance...
The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV) and two gp120 proteins (AIDSVAX B E) was previously shown to have 31.2% efficacy rate. Plasma specimens from vaccine placebo recipients were used in an extensive set assays identify correlates HIV-1 infection risk. Of six primary variables that studied, only one displayed significant inverse correlation with risk infection: the antibody (Ab) response fusion protein containing V1 V2 regions...
Abstract The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and gp120 subtype B/subtype E (B/E) proteins demonstrated 31% efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E to increase the diversity motifs in immunogen elicit a broader antibody response enhance protection. We find that immunization rhesus macaques with pentavalent results protection 55% pentavalent-vaccine-immunized from simian–human immunodeficiency virus (SHIV) challenge. Systems serology responses...
ABSTRACT The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 vaccine trial. This outcome was unexpected, given limited ability components to induce CD8 + T-cell responses or broadly neutralizing antibodies. We vaccinated macaques an immunization regimen intended mimic trial and exposed them intrarectally a dose simian SIV mac251 that transmits few...
Abstract The emergence of variants concern, some with reduced susceptibility to COVID-19 vaccines underscores consideration for the understanding vaccine design that optimizes induction effective cellular and humoral immune responses. We assessed a SARS-CoV-2 spike-ferritin nanoparticle (SpFN) immunogen paired two distinct adjuvants, Alhydrogel ® or Army Liposome Formulation containing QS-21 (ALFQ) unique evoked signatures. Recruitment highly activated multifaceted antigen-presenting cells...
Abstract The emergence of SARS-CoV-2 variants concern (VOC) requires adequate coverage vaccine protection. We evaluated whether a spike ferritin nanoparticle (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against Alpha (B.1.1.7), and Beta (B.1.351) VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 4 week) regimens, using high (10 μg) low (0.2 dose. Animals were intranasally challenged at week 11....
Emergence of novel variants the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores need for next-generation vaccines able to elicit broad and durable immunity. Here we report evaluation a ferritin nanoparticle vaccine displaying receptor-binding domain SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination macaques using two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses reciprocal peak mean...
Ebola Zaire virus (EBO-Z) causes severe hemorrhagic fever in humans, with a high mortality rate. It is thought that vaccine against EBO-Z may have to induce both humoral and cell-mediated immune responses successfully confer protection. Because it known liposome-encapsulated antigens antibody cellular responses, we evaluated the protective efficacy of irradiated [L(EV)], which contains all native proteins. In series experiments, mice immunized intravenously L(EV) were completely protected...
ABSTRACT Bacteriophage T4 capsid is an elongated icosahedron decorated with 155 copies of Hoc, a nonessential highly antigenic outer protein. One Hoc monomer present in the center each major protein (gp23*) hexon. We describe vitro assembly system which allows display HIV antigens, p24-gag, Nef, and engineered gp41 C-peptide trimer, on phage surface through Hoc-capsid interactions. In-frame fusions were constructed by splicing human immunodeficiency virus (HIV) genes to 5′ or 3′ end gene....
The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired syndrome (AIDS) and other infectious diseases has expanded rapidly over past 8 years. Highly immunodeficient strains, such as NOD/SCID/gamma chain(null) (NSG, NOG), support better hematopoietic cell engraftment. Another improvement is derivation highly mice, transgenic with leukocyte antigens (HLAs) cytokines that supported development HLA-restricted T cells heightened myeloid Humanized mice are also...
In order to inform the rational design of HIV-1 preventive and cure interventions it is critical understand events occurring during acute infection (AHI). Using viral deep sequencing on six participants from early capture RV217 cohort, we have studied evolution in plasma collected twice weekly first weeks following advent viremia. The analysis infections established by multiple transmitted/founder (T/F) viruses revealed novel profiles that included: a) low-level persistence minor T/F...