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2. Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Author

Vaccari, Monica, Gordon, Shari N, Fourati, Slim, Schifanella, Luca, Liyanage, Namal PM, Cameron, Mark, Keele, Brandon F, Shen, Xiaoying, Tomaras, Georgia D, Billings, Erik, Rao, Mangala, Chung, Amy W, Dowell, Karen G, Bailey-Kellogg, Chris, Brown, Eric P, Ackerman, Margaret E, Vargas-Inchaustegui, Diego A, Whitney, Stephen, Doster, Melvin N, Binello, Nicolo, Pegu, Poonam, Montefiori, David C, Foulds, Kathryn, Quinn, David S, Donaldson, Mitzi, Liang, Frank, Loré, Karin, Roederer, Mario, Koup, Richard A, McDermott, Adrian, Ma, Zhong-Min, Miller, Christopher J, Phan, Tran B, Forthal, Donald N, Blackburn, Matthew, Caccuri, Francesca, Bissa, Massimiliano, Ferrari, Guido, Kalyanaraman, Vaniambadi, Ferrari, Maria G, Thompson, DeVon, Robert-Guroff, Marjorie, Ratto-Kim, Silvia, Kim, Jerome H, Michael, Nelson L, Phogat, Sanjay, Barnett, Susan W, Tartaglia, Jim, Venzon, David, Stablein, Donald M, Alter, Galit, Sekaly, Rafick-Pierre, and Franchini, Genoveffa

Subjects
Biomedical and Clinical Sciences, Immunology, Good Health and Well Being, Adaptive Immunity, Adjuvants, Immunologic, Alum Compounds, Animals, Immunity, Innate, Immunity, Mucosal, Immunogenicity, Vaccine, Immunoglobulin G, Interleukin-17, Lymphocytes, Macaca mulatta, Membrane Glycoproteins, Random Allocation, SAIDS Vaccines, Signal Transduction, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, Transcriptome, Viral Envelope Proteins, Viral Vaccines, ras Proteins, Simian immunodeficiency virus, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.

Published
2016

4. Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research

Author

Wieczorek, Lindsay, Krebs, Shelly J, Kalyanaraman, Vaniambadi, Whitney, Stephen, Tovanabutra, Sodsai, Moscoso, Carlos G, Sanders-Buell, Eric, Williams, Constance, Slike, Bonnie, Molnar, Sebastian, Dussupt, Vincent, Alam, S Munir, Chenine, Agnes-Laurence, Tong, Tina, Hill, Edgar L, Liao, Hua-Xin, Hoelscher, Michael, Maboko, Leonard, Zolla-Pazner, Susan, Haynes, Barton F, Pensiero, Michael, McCutchan, Francine, Malek-Salehi, Shawyon, Cheng, R Holland, Robb, Merlin L, VanCott, Thomas, Michael, Nelson L, Marovich, Mary A, Alving, Carl R, Matyas, Gary R, Rao, Mangala, and Polonis, Victoria R

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Vaccine Related, Infectious Diseases, Biotechnology, Prevention, Immunization, Vaccine Related (AIDS), HIV/AIDS, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, AIDS Vaccines, Animals, Drug Evaluation, Preclinical, HIV Antibodies, HIV Infections, HIV-1, Humans, Leukocytes, Mononuclear, Molecular Sequence Data, Neutralization Tests, Rabbits, Vaccination, env Gene Products, Human Immunodeficiency Virus, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

UnlabelledEliciting broadly reactive functional antibodies remains a challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by variations in envelope (Env) subtype and structure. The majority of new global HIV-1 infections are subtype C, and novel antigenic properties have been described for subtype C Env proteins. Thus, an HIV-1 subtype C Env protein (CO6980v0c22) from an infected person in the acute phase (Fiebig stage I/II) was developed as a research reagent and candidate immunogen. The gp145 envelope is a novel immunogen with a fully intact membrane-proximal external region (MPER), extended by a polylysine tail. Soluble gp145 was enriched for trimers that yielded the expected "fan blade" motifs when visualized by cryoelectron microscopy. CO6980v0c22 gp145 reacts with the 4E10, PG9, PG16, and VRC01 HIV-1 neutralizing monoclonal antibodies (MAbs), as well as the V1/V2-specific PGT121, 697, 2158, and 2297 MAbs. Different gp145 oligomers were tested for immunogenicity in rabbits, and purified dimers, trimers, and larger multimers elicited similar levels of cross-subtype binding and neutralizing antibodies to tier 1 and some tier 2 viruses. Immunized rabbit sera did not neutralize the highly resistant CO6980v0c22 pseudovirus but did inhibit the homologous infectious molecular clone in a peripheral blood mononuclear cell (PBMC) assay. This Env is currently in good manufacturing practice (GMP) production to be made available for use as a clinical research tool and further evaluation as a candidate vaccine.ImportanceAt present, the product pipeline for HIV vaccines is insufficient and is limited by inadequate capacity to produce large quantities of vaccine to standards required for human clinical trials. Such products are required to evaluate critical questions of vaccine formulation, route, dosing, and schedule, as well as to establish vaccine efficacy. The gp145 Env protein presented in this study forms physical trimers, binds to many of the well-characterized broad neutralizing MAbs that target conserved Env epitopes, and induce cross-subtype neutralizing antibodies as measured in both cell line and primary cell assays. This subtype C Env gp145 protein is currently undergoing good manufacturing practice production for use as a reagent for preclinical studies and for human clinical research. This product will serve as a reagent for comparative studies and may represent a next-generation candidate HIV immunogen.

Published
2015

6. Evolution of Neutralization Response in HIV-1 Subtype C-Infected Individuals Exhibiting Broad Cross-Clade Neutralization of HIV-1 Strains

Author

Narayanaiah Cheedarla, Babu Hemalatha, Brahmaiah Anangi, Kannan Muthuramalingam, Murugesan Selvachithiram, Pattabiraman Sathyamurthi, Nandagopal Kailasam, Raghavan Varadarajan, Soumya Swaminathan, Srikanth Prasad Tripathy, S. Kalyanaraman Vaniambadi, D. Ramanathan Vadakkupattu, and Luke Elizabeth Hanna

Subjects
human immunodeficiency virus type 1, broadly neutralizing antibodies, Indian HIV-1 subtype C infection, evolution of neutralization response, CD4-binding site, glycan-dependent neutralization, Immunologic diseases. Allergy, RC581-607
Abstract

Strain-specific neutralizing antibodies develop in all human immunodeficiency virus type 1 (HIV-1)-infected individuals. However, only 10–30% of infected individuals produce broadly neutralizing antibodies (bNAbs). Identification and characterization of these bNAbs and understanding their evolution dynamics are critical for obtaining useful clues for the development of an effective HIV vaccine. Very recently, we published a study in which we identified 12 HIV-1 subtype C-infected individuals from India whose plasma showed potent and broad cross-clade neutralization (BCN) ability (1). In the present study, we report our findings on the evolution of host bNAb response over a period of 4 years in a subset of these individuals. Three of the five individuals (NAB033, NAB059, and NAB065) demonstrated a significant increase (p 350 cells/mm3) and continued to remain ART-naïve for more than 10 years after initial diagnosis, implying a strong clinical correlation with the development and evolution of broadly neutralizing antibody response against HIV-1.

Published
2018
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7. Unsung Hero Robert C. Gallo

Author

Abbadessa, Giovanni, Accolla, Roberto, Aiuti, Fernando, Albini, Adriana, Aldovini, Anna, Alfano, Massimo, Antonelli, Guido, Bartholomew, Courtenay, Bentwich, Zvi, Bertazzoni, Umberto, Berzofsky, Jay A., Biberfeld, Peter, Boeri, Enzo, Buonaguro, Luigi, Buonaguro, Franco M., Bukrinsky, Michael, Burny, Arsène, Caruso, Arnaldo, Cassol, Sharon, Chandra, Prakash, Ceccherini-Nelli, Luca, Chieco-Bianchi, Luigi, Clerici, Mario, Colombini-Hatch, Sandra, de Giuli Morghen, Carlo, de Maria, Andrea, de Rossi, Anita, Dierich, Manfred, Della-Favera, Riccardo, Dolei, Antonina, Douek, Daniel, Erfle, Volker, Felber, Barbara, Fiorentin, Simona, Franchini, Genoveffa, Gershoni, Jonathan M., Gotch, Frances, Green, Patrick, Greene, Warner C., Hall, William, Haseltine, William, Jacobson, Stephens, Kallings, Lars O., Kalyanaraman, Vaniambadi S., Katinger, Hermann, Khalili, Kamel, Klein, George, Klein, Eva, Klotman, Mary, Klotman, Paul, Kotler, Moshe, Kurth, Reinhard, Lafeuillade, Alain, la Placa, Michelangelo, Lewis, Jonathan, Lillo, Flavia, Lisziewicz, Julianna, Lomonico, Anita, Lopalco, Lucia, Lor, Franco, Lusso, Paolo, Macchi, Beatrice, Malim, Michael, Margolis, Leonid, Markham, Phillip D., McClure, Myra, Miller, Nancy, Mingari, Maria C., Moretta, Lorenzo, Noonan, Douglas, O'Brien, Steve, Okamoto, Takashi, Pal, Ranajit, Palese, Peter, Panet, Amos, Pantaleo, Giuseppe, Pavlakis, George, Pistello, Mauro, Plotkin, Stanley, Poli, Guido, Pomerantz, Roger, Radaelli, Antonia, Robert-Guroff, Marjorie, Roederer, Mario, Sarangadharan, Mangalasseril G., Schols, Dominique, Secchiero, Paola, Shearer, Gene, Siccardi, Antonio, Stevenson, Mario, Svoboda, Jan, Tartaglia, Jim, Torelli, Giuseppe, Tornesello, Maria Lina, Tschachler, Erwin, Vaccarezza, Mauro, Vallbracht, Angelika, van Lunzen, Jan, Varnier, Oliviero, Vicenzi, Elisa, von Melchner, Harald, Witz, Issac, Zagury, Daniel, Zagury, Jean-Francois, Zauli, Giorgio, and Zipeto, Donato

Published
2009

9. Mapping of Neutralizing Antibody Epitopes on the Envelope of Viruses Obtained from Plasma Samples Exhibiting Broad Cross-Clade Neutralization Potential Against HIV-1

Author

Manohar Nesakumar, D. Vadakkupattu Ramanathan, S. Kalyanaraman Vaniambadi, Babu Hemalatha, Jagadish Chandrabose Sundaramurthi, Manickam Ashokkumar, Brahmaiah Anangi, Luke Elizabeth Hanna, Srikanth Tripathy, Soumya Swaminathan, K. K. Vidya Vijayan, and Narayanaiah Cheedarla

Subjects
Adult, Male, 0301 basic medicine, Glycan, In silico, Immunology, HIV Infections, HIV Antibodies, Epitope, Neutralization, HIV Envelope Protein gp160, Epitopes, 03 medical and health sciences, 0302 clinical medicine, Viral envelope, Virology, Humans, 030212 general & internal medicine, Binding site, Neutralizing antibody, Vaccines, biology, Sequence Analysis, DNA, Middle Aged, Antibodies, Neutralizing, 030104 developmental biology, Infectious Diseases, HIV-1, biology.protein, Female, Antibody, Epitope Mapping
Abstract

Several broadly neutralizing antibodies (bNAbs) that can target HIV strains with large degrees of variability have recently been identified. However, efforts to induce synthesis of such bNAbs that can protect against HIV infection have not met with much success. Identification of specific epitopes encoded in the HIV-1 envelope (Env) that can direct the host to synthesize bNAbs remains a challenge. In a previous study, we identified 12 antiretroviral therapy-naive HIV-1-infected individuals whose plasma exhibited broad cross-clade neutralization property against different clades of HIV-1. In this study, we sequenced the full-length HIV-1 gp160 from 11 of these individuals and analyzed the sequences to identify bNAb epitopes. We identified critical residues in the viral envelopes that contribute to the formation of conformational epitopes and possibly induce the production of bNAbs, using in silico methods. We found that many of the sequences had conserved glycans at positions N160 (10/11) and N332 (9/11), which are known to be critical for the binding of PG9/PG16-like and PGT128-like bNAbs, respectively. We also observed conservation of critical glycans at positions N234 and N276 critical for the interaction with CD4 binding site bNAbs in 8/11 and 11/11 sequences, respectively. We modeled the three-dimensional structure of the 11 HIV-1 envelopes and found that though each had structural differences, the critical residues were mostly present on the surface of the Env structures. The identified critical residues are proposed as candidates for further evaluation as bNAb epitopes.

Published
2019

12. An adenovirus-based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains

Author

Gomez-Roman, V. Raul, Florese, Ruth H., Bo Peng, Montefiori, David C., and Kalyanaraman, Vaniambadi S.

Subjects
Adenovirus diseases -- Drug therapy, HIV infection -- Drug therapy, AIDS vaccines -- Health aspects, Health
Abstract

HIV subtype B that predominates North America and a study on ten chimpanzees regarding this protein in MF59 adjuvant is discussed. The study shows that HIV subtype B recombinant prime/envelope protein boost regimen was a good approach for eliciting broad antibody-dependent cellular cytotoxicity activity against HIV clades of diverse types.

Published
2006

14. PRIMING OF RHESUS MACAQUES WITH ALVAC-HIV-1 VACCINES VIA SYSTEMIC ROUTE FOLLOWED BY BOOSTING WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) ENVELOPE PROTEIN CONTROLS VIRE- MIA IN SYSTEMIC AND MUCOSAL COMPARTMENTS AND PROTECTS FROM LOSS OF CD4+ T-CELLS FOL- LOWING CHALLENGE WITH PATHOGENIC SHIV ISO- LATES: ABSTRACT #39

Author

Pal, Ranajit, Venzon, David, Kalyanaraman, Vaniambadi S., Montefiori, David, Hocker, Lindsey, Hudacik, Lauren, Rose, Nicolas, Nacsa, Janos, Edghill-Smith, Yvette, Belyakov, Igor, Berzofsky, Jay, Parks, Robyn Washington, Markham, Phillip, and Franchini, Genoveffa

Published
2006

15. Evolution of Neutralization Response in HIV-1 Subtype C-Infected Individuals Exhibiting Broad Cross-Clade Neutralization of HIV-1 Strains

Author

D. Ramanathan Vadakkupattu, Soumya Swaminathan, Murugesan Selvachithiram, Babu Hemalatha, Nandagopal Kailasam, Brahmaiah Anangi, Luke Elizabeth Hanna, S. Kalyanaraman Vaniambadi, Pattabiraman Sathyamurthi, Raghavan Varadarajan, Srikanth Tripathy, Narayanaiah Cheedarla, and Kannan Muthuramalingam

Subjects
lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Adult, Male, Broadly neutralizing antibody, Immunology, Human immunodeficiency virus (HIV), glycan-dependent neutralization, HIV Infections, Cross Reactions, HIV Antibodies, Clinical correlation, medicine.disease_cause, Neutralization, human immunodeficiency virus type 1, 03 medical and health sciences, medicine, Immunology and Allergy, CD4-binding site, Humans, evolution of neutralization response, HIV vaccine, Clade, Antigens, Viral, Original Research, Indian HIV-1 subtype C infection, AIDS Vaccines, 030102 biochemistry & molecular biology, biology, Immunodominant Epitopes, broadly neutralizing antibodies, Virology, Antibodies, Neutralizing, Immunity, Humoral, 030104 developmental biology, HEK293 Cells, biology.protein, HIV-1, Female, Antibody, lcsh:RC581-607, Follow-Up Studies
Abstract

Strain-specific neutralizing antibodies develop in all human immunodeficiency virus type 1 (HIV-1)-infected individuals. However, only 10–30% of infected individuals produce broadly neutralizing antibodies (bNAbs). Identification and characterization of these bNAbs and understanding their evolution dynamics are critical for obtaining useful clues for the development of an effective HIV vaccine. Very recently, we published a study in which we identified 12 HIV-1 subtype C-infected individuals from India whose plasma showed potent and broad cross-clade neutralization (BCN) ability (1). In the present study, we report our findings on the evolution of host bNAb response over a period of 4 years in a subset of these individuals. Three of the five individuals (NAB033, NAB059, and NAB065) demonstrated a significant increase (p 350 cells/mm3) and continued to remain ART-naïve for more than 10 years after initial diagnosis, implying a strong clinical correlation with the development and evolution of broadly neutralizing antibody response against HIV-1.

Published
2018

16. A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr: Potential impact on CTL epitopes

Author

Collman Ronald G, Cristillo Anthony, Kalyanaraman Vaniambadi S, Datta Debduti, Boyd Anne, Kannan Aarthi, Mahalingam Sundarasamy, Ayyavoo Velpandi, Srinivasan Alagarsamy, Morellet Nelly, Sawaya Bassel E, and Murali Ramachandran

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract The enormous genetic variability reported in HIV-1 has posed problems in the treatment of infected individuals. This is evident in the form of HIV-1 resistant to antiviral agents, neutralizing antibodies and cytotoxic T lymphocytes (CTLs) involving multiple viral gene products. Based on this, it has been suggested that a comprehensive analysis of the polymorphisms in HIV proteins is of value for understanding the virus transmission and pathogenesis as well as for the efforts towards developing anti-viral therapeutics and vaccines. This study, for the first time, describes an in-depth analysis of genetic variation in Vpr using information from global HIV-1 isolates involving a total of 976 Vpr sequences. The polymorphisms at the individual amino acid level were analyzed. The residues 9, 33, 39, and 47 showed a single variant amino acid compared to other residues. There are several amino acids which are highly polymorphic. The residues that show ten or more variant amino acids are 15, 16, 28, 36, 37, 48, 55, 58, 59, 77, 84, 86, 89, and 93. Further, the variant amino acids noted at residues 60, 61, 34, 71 and 72 are identical. Interestingly, the frequency of the variant amino acids was found to be low for most residues. Vpr is known to contain multiple CTL epitopes like protease, reverse transcriptase, Env, and Gag proteins of HIV-1. Based on this, we have also extended our analysis of the amino acid polymorphisms to the experimentally defined and predicted CTL epitopes. The results suggest that amino acid polymorphisms may contribute to the immune escape of the virus. The available data on naturally occurring polymorphisms will be useful to assess their potential effect on the structural and functional constraints of Vpr and also on the fitness of HIV-1 for replication.

Published
2008
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17. Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals

Author

Nandagopal Kailasam, Viswanath Buddolla, Jagadish Chandrabose Sundaramurthi, S. Kalyanaraman Vaniambadi, Manickam Ashokkumar, K. Lucia Precilla, Soumya Swaminathan, Luke Elizabeth Hanna, K. K. Vidya Vijayan, V. D. Ramanathan, Narayanaiah Cheedarla, Padmapriyadarsini Chandrasekaran, and Hemalatha Babu

Subjects
0301 basic medicine, Adult, Male, Glycan, CD4 antigen, Human immunodeficiency virus (HIV), HIV Infections, Biology, HIV Antibodies, medicine.disease_cause, Article, Epitope, Neutralization, Antibodies, Vaccine Related, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Antibody Specificity, Clinical Research, medicine, Potency, Humans, Clade, Vaccine Related (AIDS), Neutralizing, Multidisciplinary, Prevention, Middle Aged, Antibodies, Neutralizing, Virology, 030104 developmental biology, Good Health and Well Being, chemistry, biology.protein, HIV-1, HIV/AIDS, Female, Immunization, Antibody, Infection, 030215 immunology
Abstract

Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine.

Published
2017

20. Corrigendum: Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Author

Vaccari, Monica, Gordon, Shari N, Fourati, Slim, Schifanella, Luca, Liyanage, Namal P M, Cameron, Mark, Keele, Brandon F, Shen, Xiaoying, Tomaras, Georgia D, Billings, Erik, Rao, Mangala, Chung, Amy W, Dowell, Karen G, Bailey-Kellogg, Chris, Brown, Eric P, Ackerman, Margaret E, Vargas-Inchaustegui, Diego A, Whitney, Stephen, Doster, Melvin N, Binello, Nicolo, Pegu, Poonam, Montefiori, David C, Foulds, Kathryn, Quinn, David S, Donaldson, Mitzi, Liang, Frank, Loré, Karin, Roederer, Mario, Koup, Richard A, McDermott, Adrian, Ma, Zhong-Min, Miller, Christopher J, Phan, Tran B, Forthal, Donald N, Blackburn, Matthew, Caccuri, Francesca, Bissa, Massimiliano, Ferrari, Guido, Kalyanaraman, Vaniambadi, Ferrari, Maria G, Thompson, DeVon, Robert-Guroff, Marjorie, Ratto-Kim, Silvia, Kim, Jerome H, Michael, Nelson L, Phogat, Sanjay, Barnett, Susan W, Tartaglia, Jim, Venzon, David, Stablein, Donald M, Alter, Galit, Sekaly, Rafick-Pierre, and Franchini, Genoveffa

Subjects
Biological sciences, Health
Abstract

Author(s): Monica Vaccari; Shari N Gordon; Slim Fourati; Luca Schifanella; Namal P M Liyanage; Mark Cameron; Brandon F Keele; Xiaoying Shen; Georgia D Tomaras; Erik Billings; Mangala Rao; Amy W [...]

Published
2016
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21. DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant

Author

Menon, Veena, primary, Ayala, Victor I., additional, Rangaswamy, Sneha P., additional, Kalisz, Irene, additional, Whitney, Stephen, additional, Galmin, Lindsey, additional, Ashraf, Asma, additional, LaBranche, Celia, additional, Montefiori, David, additional, Petrovsky, Nikolai, additional, Kalyanaraman, Vaniambadi S., additional, and Pal, Ranajit, additional

Published
2017
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22. Erratum: Corrigendum: Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Author

Vaccari, Monica, primary, Gordon, Shari N, additional, Fourati, Slim, additional, Schifanella, Luca, additional, Liyanage, Namal P M, additional, Cameron, Mark, additional, Keele, Brandon F, additional, Shen, Xiaoying, additional, Tomaras, Georgia D, additional, Billings, Erik, additional, Rao, Mangala, additional, Chung, Amy W, additional, Dowell, Karen G, additional, Bailey-Kellogg, Chris, additional, Brown, Eric P, additional, Ackerman, Margaret E, additional, Vargas-Inchaustegui, Diego A, additional, Whitney, Stephen, additional, Doster, Melvin N, additional, Binello, Nicolo, additional, Pegu, Poonam, additional, Montefiori, David C, additional, Foulds, Kathryn, additional, Quinn, David S, additional, Donaldson, Mitzi, additional, Liang, Frank, additional, Loré, Karin, additional, Roederer, Mario, additional, Koup, Richard A, additional, McDermott, Adrian, additional, Ma, Zhong-Min, additional, Miller, Christopher J, additional, Phan, Tran B, additional, Forthal, Donald N, additional, Blackburn, Matthew, additional, Caccuri, Francesca, additional, Bissa, Massimiliano, additional, Ferrari, Guido, additional, Kalyanaraman, Vaniambadi, additional, Ferrari, Maria G, additional, Thompson, DeVon, additional, Robert-Guroff, Marjorie, additional, Ratto-Kim, Silvia, additional, Kim, Jerome H, additional, Michael, Nelson L, additional, Phogat, Sanjay, additional, Barnett, Susan W, additional, Tartaglia, Jim, additional, Venzon, David, additional, Stablein, Donald M, additional, Alter, Galit, additional, Sekaly, Rafick-Pierre, additional, and Franchini, Genoveffa, additional

Published
2016
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23. Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA Immunity in Rhesus Macaques Correlated with Delayed Acquisition following a Repeated Low-Dose Rectal SIVmac251 Challenge

Author

Xiao, Peng, Patterson, L. Jean, Kuate, Seraphin, Brocca-Cofano, Egidio, Thomas, Michael A., Venzon, David, Zhao, Jun, DiPasquale, Janet, Fenizia, Claudio, Lee, Eun Mi, Kalisz, Irene, Kalyanaraman, Vaniambadi S., Pal, Ranajit, Montefiori, David, Keele, Brandon F., and Robert-Guroff, Marjorie

Subjects
Male, Vaccines, Synthetic, Adenoviruses, Human, T-Lymphocytes, Molecular Sequence Data, Gene Products, env, chemical and pharmacologic phenomena, Antibodies, Viral, Antibodies, Neutralizing, Macaca mulatta, Antibody Specificity, Vaccines and Antiviral Agents, Immunoglobulin A, Secretory, Animals, Cytokines, Humans, Female, Simian Immunodeficiency Virus, Viremia, Immunity, Mucosal, Immunologic Memory
Abstract

We have shown that sequential replicating adenovirus type 5 host range mutant human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) recombinant priming delivered first intranasally (i.n.) plus orally and then intratracheally (i.t.), followed by envelope protein boosting, elicits broad cellular immunity and functional, envelope-specific serum and mucosal antibodies that correlate with protection from high-dose SIV and simian/human immunodeficiency virus (SHIV) challenges in rhesus macaques. Here we extended these studies to compare the standard i.n./i.t. regimen with additional mucosal administration routes, including sublingual, rectal, and vaginal routes. Similar systemic cellular and humoral immunity was elicited by all immunization routes. Central and effector memory T cell responses were also elicited by the four immunization routes in bronchoalveolar lavage fluid and jejunal, rectal, and vaginal tissue samples. Cellular responses in vaginal tissue were more compartmentalized, being induced primarily by intravaginal administration. In contrast, all immunization routes elicited secretory IgA (sIgA) responses at multiple mucosal sites. Following a repeated low-dose intrarectal (i.r.) challenge with SIV(mac251) at a dose transmitting one or two variants, protection against acquisition was not achieved except in one macaque in the i.r. immunized group. All immunized macaques exhibited reduced peak viremia compared to that of controls, correlated inversely with prechallenge serum antienvelope avidity, antibody-dependent cellular cytotoxicity (ADCC) titers, and percent antibody-dependent cell-mediated viral inhibition. Both antibody avidity and ADCC titers were correlated with the number of exposures required for infection. Notably, we show for the first time a significant correlation of vaccine-induced sIgA titers in rectal secretions with delayed acquisition. Further investigation of the characteristics and properties of the sIgA should elucidate the mechanism leading to this protective effect.

Published
2012

24. Antigenicity and Immunogenicity of a Trimeric Envelope Protein from an Indian Clade C HIV-1 Isolate

Author

Sneha Priya, Rangasamy, primary, Veena, Menon, additional, Kalisz, Irene, additional, Whitney, Stephen, additional, Priyanka, Dhopeshwarkar, additional, LaBranche, Celia C., additional, Sri Teja, Mullapudi, additional, Montefiori, David C., additional, Pal, Ranajit, additional, Mahalingam, Sundarasamy, additional, and Kalyanaraman, Vaniambadi S., additional

Published
2015
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25. Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA Immunity in Rhesus Macaques Correlated with Delayed Acquisition following a Repeated Low-Dose Rectal SIV mac251 Challenge

Author

Xiao, Peng, primary, Patterson, L. Jean, additional, Kuate, Seraphin, additional, Brocca-Cofano, Egidio, additional, Thomas, Michael A., additional, Venzon, David, additional, Zhao, Jun, additional, DiPasquale, Janet, additional, Fenizia, Claudio, additional, Lee, Eun Mi, additional, Kalisz, Irene, additional, Kalyanaraman, Vaniambadi S., additional, Pal, Ranajit, additional, Montefiori, David, additional, Keele, Brandon F., additional, and Robert-Guroff, Marjorie, additional

Published
2012
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27. Correlation of Vaccine-Elicited Systemic and Mucosal Nonneutralizing Antibody Activities with Reduced Acute Viremia following Intrarectal Simian Immunodeficiency Virus SIV mac251 Challenge of Rhesus Macaques

Author

Hidajat, Rachmat, primary, Xiao, Peng, additional, Zhou, Qifeng, additional, Venzon, David, additional, Summers, L. Ebonita, additional, Kalyanaraman, Vaniambadi S., additional, Montefiori, David C., additional, and Robert-Guroff, Marjorie, additional

Published
2009
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29. A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr: Potential impact on CTL epitopes

Author

Srinivasan, Alagarsamy, primary, Ayyavoo, Velpandi, additional, Mahalingam, Sundarasamy, additional, Kannan, Aarthi, additional, Boyd, Anne, additional, Datta, Debduti, additional, Kalyanaraman, Vaniambadi S, additional, Cristillo, Anthony, additional, Collman, Ronald G, additional, Morellet, Nelly, additional, Sawaya, Bassel E, additional, and Murali, Ramachandran, additional

Published
2008
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30. HIV-1 prophylactic vaccine comprised of topical DermaVir prime and protein boost elicits cellular immune responses and controls pathogenic R5 SHIV162P3

Author

Cristillo, Anthony D., primary, Lisziewicz, Julianna, additional, He, Leilei, additional, Lori, Franco, additional, Galmin, Lindsey, additional, Trocio, Jeffrey N., additional, Unangst, Tami, additional, Whitman, Lucia, additional, Hudacik, Lauren, additional, Bakare, Nyasha, additional, Whitney, Stephen, additional, Restrepo, Susana, additional, Suschak, John, additional, Grazi Ferrari, Maria, additional, Chung, H.K., additional, Kalyanaraman, Vaniambadi S., additional, Markham, Phillip, additional, and Pal, Ranajit, additional

Published
2007
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31. An Adenovirus-Based HIV Subtype B Prime/Boost Vaccine Regimen Elicits Antibodies Mediating Broad Antibody-Dependent Cellular Cytotoxicity Against Non-Subtype B HIV Strains

Author

G??mez-Rom??n, V. Ra??l, primary, Florese, Ruth H, additional, Peng, Bo, additional, Montefiori, David C, additional, Kalyanaraman, Vaniambadi S, additional, Venzon, David, additional, Srivastava, Indresh, additional, Barnett, Susan W, additional, and Robert-Guroff, Marjorie, additional

Published
2006
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32. Evaluation of Passively Transferred, Nonneutralizing Antibody-Dependent Cellular Cytotoxicity-Mediating IgG in Protection of Neonatal Rhesus Macaques against Oral SIVmac251 Challenge

Author

Florese, Ruth H., primary, Van Rompay, Koen K. A., additional, Aldrich, Kris, additional, Forthal, Donald N., additional, Landucci, Gary, additional, Mahalanabis, Madhumita, additional, Haigwood, Nancy, additional, Venzon, David, additional, Kalyanaraman, Vaniambadi S., additional, Marthas, Marta L., additional, and Robert-Guroff, Marjorie, additional

Published
2006
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33. Subunit Recombinant Vaccine Protects against Monkeypox

Author

Heraud, Jean-Michel, primary, Edghill-Smith, Yvette, additional, Ayala, Victor, additional, Kalisz, Irene, additional, Parrino, Janie, additional, Kalyanaraman, Vaniambadi S., additional, Manischewitz, Jody, additional, King, Lisa R., additional, Hryniewicz, Anna, additional, Trindade, Christopher J., additional, Hassett, Meredith, additional, Tsai, Wen-Po, additional, Venzon, David, additional, Nalca, Aysegul, additional, Vaccari, Monica, additional, Silvera, Peter, additional, Bray, Mike, additional, Graham, Barney S., additional, Golding, Hana, additional, Hooper, Jay W., additional, and Franchini, Genoveffa, additional

Published
2006
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34. Systemic Immunization with an ALVAC-HIV-1/Protein Boost Vaccine Strategy Protects Rhesus Macaques from CD4 + T-Cell Loss and Reduces both Systemic and Mucosal Simian-Human Immunodeficiency Virus SHIV KU2 RNA Levels

Author

Pal, Ranajit, primary, Venzon, David, additional, Santra, Sampa, additional, Kalyanaraman, Vaniambadi S., additional, Montefiori, David C., additional, Hocker, Lindsey, additional, Hudacik, Lauren, additional, Rose, Nicolas, additional, Nacsa, Janos, additional, Edghill-Smith, Yvette, additional, Moniuszko, Marcin, additional, Hel, Zdeněk, additional, Belyakov, Igor M., additional, Berzofsky, Jay A., additional, Parks, Robyn Washington, additional, Markham, Phillip D., additional, Letvin, Norman L., additional, Tartaglia, Jim, additional, and Franchini, Genoveffa, additional

Published
2006
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35. Preclinical evaluation of cellular immune responses elicited by a polyvalent DNA prime/protein boost HIV-1 vaccine

Author

Cristillo, Anthony D., primary, Wang, Shixia, additional, Caskey, Michael S., additional, Unangst, Tami, additional, Hocker, Lindsey, additional, He, Leilei, additional, Hudacik, Lauren, additional, Whitney, Stephen, additional, Keen, Tim, additional, Chou, Te-hui W., additional, Shen, Siyuan, additional, Joshi, Swati, additional, Kalyanaraman, Vaniambadi S., additional, Nair, Balachandran, additional, Markham, Phillip, additional, Lu, Shan, additional, and Pal, Ranajit, additional

Published
2006
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