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1. IFNL4 genotype influences the rate of HIV-1 seroconversion in men who have sex with men

Author

Meza, Giovanna, Galián, Fátima, Jaimes-Bernal, Claudia, Márquez, Francisco J, Sinangil, Faruk, Scagnolari, Carolina, Real, Luis Miguel, Forthal, Donald, and Caruz, Antonio

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, HIV/AIDS, Infectious Diseases, Genetics, Prevention, Infection, Good Health and Well Being, Genotype, HIV Infections, HIV-1, Homosexuality, Male, Humans, Interferons, Interleukins, Male, Seroconversion, Sexual and Gender Minorities, HESN, HIV exposed seronegative, IFNL4, IL28B, Ecological Applications, Microbiology, Medical microbiology
Abstract

Individuals lacking interferon lambda 4 (IFNL4) protein due to a common null mutation (rs368234815) in the IFNL4 gene display higher resistance against several infections. The influence of IFNL4 on HIV-1 infection is still under discussion and conflicting results have been reported. This study intended to corroborate or refute the association of the null allele of IFNL4 and HIV-1 predisposition in a cohort of men who have sex with men (MSM). IFNL4 null genotype was assessed on 619 HIV-1-seronegative MSM who were followed for 36 months during a trial of a prophylactic vaccine against HIV-1. Of those, 257 individuals seroconverted during this period. A logistic regression model was constructed including demographic and IFNL4 genotype. In addition, a meta-analysis using data from the current study and other European populations was conducted. The null IFNL4 genotypes were correlated with lower HIV-1 seroconversion (Adjusted OR = 0.4 [95%CI: 0.2-0.8], P = 0.008) and longer time to seroconversion (889 vs. 938 days, P= 0.01). These results were validated by a meta-analysis incorporating data from other European populations and the result yielded a significant association of the IFNL4 null genotype under a dominant model with a lower probability of HIV-1 infection (OR=0.4 [95% CI: 0.3-0.6]; P= 1.3 x 10E-5).

Published
2022

2. No association of a risk variant for severe COVID-19 with HIV protection in three cohorts of highly exposed individuals.

Author

Sironi, Manuela, Cagliani, Rachele, Biasin, Mara, Lo Caputo, Sergio, Saulle, Irma, Forni, Diego, Real, Luis, Pineda, Juan, Exposito, Almudena, Saez, María, Sinangil, Faruk, Forthal, Donald, Caruz, Antonio, and Clerici, Mario

Subjects
COVID-19, HIV, exposed seronegative individuals, genetic risk factor
Abstract

An extended haplotype on chromosome 3 is the major genetic risk factor for severe COVID-19. The risk haplotype, which was inherited from Neanderthals, decreases the expression of several cytokine receptors, including CCR5. Recently, a study based on three general population cohorts indicated that the minor allele of one of the variants in the haplotype (rs17713054) protects against HIV infection. We thus expected this allele to be over-represented in highly exposed individuals who remain uninfected (exposed seronegative individuals, ESN). To perform a meta-analysis, we genotyped rs17713054 in three ESN cohorts of European ancestry exposed to HIV through different routes. No evidence of association was detected in the single cohorts. The meta-analysis also failed to detect any effect of the variant on protection from HIV-1. The same results were obtained in a Cox-regression analysis for the time to seroconversion. An in-vitro infection assay did not detect differences in viral replication as a function of rs17713054 genotype status. We conclude that the rs17713054 minor allele is not associated with the ESN phenotype and does not modulate HIV infection in vitro.

Published
2022

4. Ancestral sequences from an elite neutralizer proximal to the development of neutralization resistance as a potential source of HIV vaccine immunogens

Author

Mesa, Kathryn A, Yu, Bin, Wrin, Terri, Petropoulos, Christos J, Pogson, Grant H, Alexander, David L, Perez, Gerardo, O’Rourke, Sara M, Sinangil, Faruk, Robinson, Joseph, Conant, Marcus A, and Berman, Phillip W

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Vaccine Related, Immunization, Infectious Diseases, Biotechnology, Vaccine Related (AIDS), HIV/AIDS, Prevention, Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Infection, Good Health and Well Being, AIDS Vaccines, Broadly Neutralizing Antibodies, Epitopes, HIV, HIV Antibodies, HIV Antigens, HIV Infections, Humans, Immunogenicity, Vaccine, Neutralization Tests, Phylogeny, Proviruses, env Gene Products, Human Immunodeficiency Virus, General Science & Technology
Abstract

A major challenge in HIV vaccine development is the identification of immunogens able to elicit broadly neutralizing antibodies (bNAbs). While remarkable progress has been made in the isolation and characterization of bNAbs, the epitopes they recognize appear to be poorly immunogenic. Thus, none of the candidate vaccines developed to date has induced satisfactory levels of neutralizing antibodies to the HIV envelope protein (Env). One approach to the problem of poor immunogenicity is to build vaccines based on envelope (env) genes retrieved from rare individuals termed elite neutralizers (ENs) who at one time possessed specific sequences that stimulated the formation of bNAbs. Env proteins selected from these individuals could possess uncommon, yet to be defined, structural features that enhance the immunogenicity of epitopes recognized by bNAbs. Here we describe the recovery of envs from an EN that developed unusually broad and potent bNAbs. As longitudinal specimens were not available, we combined plasma and provirus sequences acquired from a single time-point to infer a phylogenetic tree. Combining ancestral reconstruction data with virus neutralization data allowed us to sift through the myriad of virus quasi-species that evolved in this individual to identify envelope sequences from the nodes that appeared to define the transition from neutralization sensitive envs to the neutralization resistant envs that occur in EN plasma. Synthetic genes from these nodes were functional in infectivity assays and sensitive to neutralization by bNAbs, and may provide a novel source of immunogens for HIV vaccine development.

Published
2019

5. Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production

Author

N’guessan, Kombo F., primary, Machmach, Kawthar, additional, Swafford, Isabella, additional, Costanzo, Margaret C., additional, Wieczorek, Lindsay, additional, Kim, Dohoon, additional, Akapirat, Siriwat, additional, Polonis, Victoria R., additional, Pitisuttithum, Punnee, additional, Nitayaphan, Sorachai, additional, Gurunathan, Sanjay, additional, Sinangil, Faruk, additional, Chariyalertsak, Suwat, additional, Ake, Julie A., additional, O’connell, Robert J., additional, Vasan, Sandhya, additional, and Paquin-Proulx, Dominic, additional

Published
2024
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6. Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial

Author

Pitisuthitham, Arom, Sabmee, Yupa, Sirisopana, Narongrid, Eamsila, Chirapa, Savaraj, Prapaporn, Labwech, Wanlaya, Teerachia, Siriluck, Chotirosniramit, Nuntisa, Supindham, Taweewat, Pruenglampoo, Boonlure, Sugandhavesa, Patcharaphan, Kosashunhanan, Natthapol, Kaewthip, Oranitcha, Sroysuwan, Piyathida, Jarujareet, Pawinee, Ratto-Kim, Silvia, Molnar, Sebastian, Schoen, Jesse, Churikanont, Nampueng, Getchalarat, Saowanit, Sangnoi, Nongluck, Nuntapinit, Bessara, Phramtong, Anant, Grandin, Pornsuk V., Madnote, Sirinan, Rittiroongrad, Surawach, Kaewboon, Boot, Trichavaroj, Rapee, Puangkaew, Jiraporn, Chantakulkij, Somsak, Rakyat, Phiromrat, Panjapornsuk, Pornchanok, Tragonlugsana, Nipattra, Chuenarom, Weerawan, de Souza, Mark, Ngauy, Viseth, Phanuphak, Nittaya, Chomchey, Nitiya, Saengtawan, Puttachard, Teeratakulpisarn, Nipat, Rerknimitr, Rungsun, Kroon, Eugene, Lee, Carter A., Chinaworapong, Suchada, Pitisuttithum, Punnee, Nitayaphan, Sorachai, Chariyalertsak, Suwat, Kaewkungwal, Jaranit, Dawson, Peter, Dhitavat, Jittima, Phonrat, Benjaluck, Akapirat, Siriwat, Karasavvas, Nicos, Wieczorek, Lindsay, Polonis, Victoria, Eller, Michael A, Pegu, Poonam, Kim, Dohoon, Schuetz, Alexandra, Jongrakthaitae, Surat, Zhou, Yingjun, Sinangil, Faruk, Phogat, Sanjay, Diazgranados, Carlos A, Tartaglia, James, Heger, Elizabeth, Smith, Kirsten, Michael, Nelson L, Excler, Jean-Louis, Robb, Merlin L, Kim, Jerome H, O'Connell, Robert J, and Vasan, Sandhya

Published
2020
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7. DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial

Author

Rouphael, Nadine G., Morgan, Cecilia, Li, Shuying S., Jensen, Ryan, Sanchez, Brittany, Karuna, Shelly, Swann, Edith, Sobieszczyk, Magdalena E., Frank, an, Wilson, Gregory J., Tieu, Hong-Van, Maenza, Janine, Norwood, Aliza, Kobie, James, Sinangil, Faruk, Pantaleo, Giuseppe, Ding, Song, McElrath, M. Juliana, De Rosa, Stephen C., Montefiori, David C., Ferrari, Guido, Tomaras, Georgia D., and Keefer, Michael C.

Subjects
United States. National Institute of Allergy and Infectious Diseases, Clinical trials, AIDS vaccines -- Research, Combination drug therapy, HIV -- Research, DNA, Vaccination, Immune response, Immunoglobulin G, T cells, Vaccines, Allergy, Antibodies, Research funding, Communicable diseases, Health care industry
Abstract

BACKGROUND. RV144 is the only preventive HIV vaccine regimen demonstrating efficacy in humans. Attempting to build upon RV144 immune responses, we conducted a phase 1, multicenter, randomized, double-blind trial to assess the safety and immunogenicity of regimens substituting the DNA-HIV-PT123 (DNA) vaccine for ALVAC-HIV in different sequences or combinations with AIDSVAX B/E (protein). METHODS. One hundred and four HIV-uninfected participants were randomized to 4 treatment groups (T1, T2, T3, and T4) and received intramuscular injections at 0, 1, 3, and 6 months (M): T1 received protein at M0 and M1 and DNA at M3 and M6; T2 received DNA at M0 and M1 and protein at M3 and M6; T3 received DNA at M0, M1, M3, and M6 with protein coadministered at M3 and M6; and T4 received protein and DNA coadministered at each vaccination visit. RESULTS. All regimens were well tolerated. Antibodies binding to gp120 and V1V2 scaffold were observed in 95%-100% of participants in T3 and T4, two weeks after final vaccination at high magnitude. While IgG3 responses were highest in T3, a lower IgA/IgG ratio was observed in T4. Binding antibodies persisted at 12 months in 35%-100% of participants. Antibody-dependent cell-mediated cytotoxicity and tier 1 neutralizing-antibody responses had higher response rates for T3 and T4, respectively. [CD4.sup.+] T cell responses were detectable in all treatment groups (32%-64%) without appreciable [CD8.sup.+] T cell responses. CONCLUSION. The DNA/protein combination regimens induced high-magnitude and long-lasting HIV V1V2-binding antibody responses, and early coadministration of the 2 vaccines led to a more rapid induction of these potentially protective responses. TRIAL REGISTRATION. ClinicalTrials.gov NCT02207920. FUNDING. National Institute of Allergy and Infectious Diseases (NIAID) grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069511, UM1 AI069470, UM1 AI069534, P30 AI450008, UM1 AI069439, UM1 AI069481, and UM1 AI069496; the National Center for Advancing Translational Sciences, NIH (grant UL1TR001873); and the Bill & Melinda Gates Foundation (grant OPP52845)., Introduction Almost 40 million people are living with HIV worldwide. Every year, there are 1.8 million new infections and 1.2 million deaths from HIV-related causes (1), making the need for [...]

Published
2019
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8. Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production.

Author

N'guessan, Kombo F., Machmach, Kawthar, Swafford, Isabella, Costanzo, Margaret C., Wieczorek, Lindsay, Dohoon Kim, Akapirat, Siriwat, Polonis, Victoria R., Punnee Pitisuttithum, Nitayaphan, Sorachai, Gurunathan, Sanjay, Sinangil, Faruk, Suwat Chariyalertsak, Ake, Julie A., O'connell, Robert J., Vasan, Sandhya, and Paquin-Proulx, Dominic

Subjects
ANTIBODY formation, KILLER cells, CLINICAL trials, THAI people, T cells
Abstract

The RV144 Thai phase III clinical trial's canarypox-protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIVuninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vd1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Randomized, Double-Blind Evaluation of Late Boost Strategies for HIV-Uninfected Vaccine Recipients in the RV 144 HIV Vaccine Efficacy Trial

Author

RV305 Study Team, Rerks-Ngarm, Supachai, Pitisuttithum, Punnee, Excler, Jean-Louis, Nitayaphan, Sorachai, Kaewkungwal, Jaranit, Premsri, Nakorn, Kunasol, Prayura, Karasavvas, Nicos, Schuetz, Alexandra, Ngauy, Viseth, Sinangil, Faruk, Dawson, Peter, deCamp, Allan C., Phogat, Sanjay, Garunathan, Sanjay, Tartaglia, James, DiazGranados, Carlos, Ratto-Kim, Silvia, Pegu, Poonam, Eller, Michael, Karnasuta, Chitraporn, Montefiori, David C., Sawant, Sheetal, Vandergrift, Nathan, Wills, Saintedym, Tomaras, Georgia D., Robb, Merlin L., Michael, Nelson L., Kim, Jerome H., Vasan, Sandhya, and O'Connell, Robert J.

Published
2017

10. Novel Ring Structure in the gp41 Trimer of Human Immunodeficiency Virus Type 1 That Modulates Sensitivity and Resistance to Broadly Neutralizing Antibodies▿ †

Author

O'Rourke, Sara M, Schweighardt, Becky, Scott, William G, Wrin, Terri, Fonseca, Dora PAJ, Sinangil, Faruk, and Berman, Phillip W

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Immunization, Prevention, Vaccine Related, Vaccine Related (AIDS), Infectious Diseases, Sexually Transmitted Infections, HIV/AIDS, Infection, Good Health and Well Being, Amino Acid Sequence, Antibodies, Viral, HIV Envelope Protein gp41, HIV Infections, HIV-1, Humans, Molecular Conformation, Molecular Sequence Data, Mutation, Neutralization Tests, Protein Conformation, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

The identification of the determinants of sensitivity and resistance to broadly neutralizing antibodies is a high priority for human immunodeficiency virus (HIV) research. An analysis of the swarm of closely related envelope protein variants in an HIV-infected individual revealed a mutation that markedly affected sensitivity to neutralization by antibodies and antiviral entry inhibitors targeting both gp41 and gp120. This mutation mapped to the C34 helix of gp41 and disrupted an unexplored structural feature consisting of a ring of hydrogen bonds in the gp41 trimer. This mutation appeared to affect the assembly of the six-helix bundle required for virus fusion and to alter the conformational equilibria so as to favor the prehairpin intermediate conformation required for the binding of the membrane proximal external region-specific neutralizing antibodies 2F5 and 4E10 and the antiviral drug enfuvirtide (Fuzeon). The "swarm analysis" method we describe furthers our understanding of the relationships among the structure, function, and antigenicity of the HIV envelope protein and represents a new approach to the identification of vaccine antigens.

Published
2009

11. ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone

Author

Costanzo, Margaret C., primary, Paquin-Proulx, Dominic, additional, Schuetz, Alexandra, additional, Akapirat, Siriwat, additional, Shubin, Zhanna, additional, Kim, Dohoon, additional, Wieczorek, Lindsay, additional, Polonis, Victoria R., additional, Trinh, Hung V., additional, Rao, Mangala, additional, Anenia, Hanna, additional, Barrera, Michael D., additional, Boeckelman, Jacob, additional, Nails, Barbara, additional, Thapa, Pallavi, additional, Zemil, Michelle, additional, Sacdalan, Carlo, additional, Kroon, Eugene, additional, Kaewboon, Boot, additional, Tipsuk, Somporn, additional, Jongrakthaitae, Surat, additional, Gurunathan, Sanjay, additional, Sinangil, Faruk, additional, Kim, Jerome H., additional, Robb, Merlin L., additional, Ake, Julie A., additional, O’Connell, Robert J., additional, Pitisutthithum, Punnee, additional, Nitayaphan, Sorachai, additional, Chariyalertsak, Suwat, additional, Eller, Michael A., additional, Phanuphak, Nittaya, additional, and Vasan, Sandhya, additional

Published
2023
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13. Differential induction of anti-V3 crown antibodies with cradle- and ladle-binding modes in response to HIV-1 envelope vaccination

Author

Balasubramanian, Preetha, Kumar, Rajnish, Williams, Constance, Itri, Vincenza, Wang, Shixia, Lu, Shan, Hessell, Ann J., Haigwood, Nancy L., Sinangil, Faruk, Higgins, Keith W., Liu, Lily, Li , Liuzhe, Nyambi, Phillipe, Gorny, Miroslaw K., Totrov, Maxim, Nadas, Arthur, Kong, Xiang-Peng, Zolla-Pazner, Susan, and Hioe, Catarina E.

Published
2017
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15. Magnitude and Breadth of the Neutralizing Antibody Response in the RV144 and Vax003 HIV-1 Vaccine Efficacy Trials

Author

Montefiori, David C., Karnasuta, Chitraporn, Huang, Ying, Ahmed, Hasan, Gilbert, Peter, de Souza, Mark S., McLinden, Robert, Tovanabutra, Sodsai, Laurence-Chenine, Agnes, Sanders-Buell, Eric, Moody, M. Anthony, Bonsignori, Mattia, Ochsenbauer, Christina, Kappes, John, Tang, Haili, Greene, Kelli, Gao, Hongmei, LaBranche, Celia C., Andrews, Charla, Polonis, Victoria R., Rerks-Ngarm, Supachai, Pitisuttithum, Punnee, Nitayaphan, Sorachai, Kaewkungwal, Jaranit, Self, Steve G., Berman, Phillip W., Francis, Donald, Sinangil, Faruk, Lee, Carter, Tartaglia, Jim, Robb, Merlin L., Haynes, Barton F., Michael, Nelson L., and Kim, Jerome H.

Published
2012
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21. AIDSVAX protein boost improves breadth and magnitude of vaccine-induced HIV-1 envelope-specific responses after a 7-year rest period

Author

Huang, Yunda, primary, Seaton, Kelly E., additional, Casapia, Martin, additional, Polakowski, Laura, additional, De Rosa, Stephen C., additional, Cohen, Kristen, additional, Yu, Chenchen, additional, Elizaga, Marnie, additional, Paez, Carmen, additional, Miner, Maurine D., additional, Kelley, Colleen F., additional, Maenza, Janine, additional, Keefer, Michael, additional, Lama, Javier R., additional, Sobieszczyk, Magdalena, additional, Buchbinder, Susan, additional, Baden, Lindsey R., additional, Lee, Carter, additional, Gulati, Vineeta, additional, Sinangil, Faruk, additional, Montefiori, David, additional, McElrath, M. Juliana, additional, Tomaras, Georgia D., additional, Robinson, Harriet L., additional, and Goepfert, Paul, additional

Published
2021
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22. Human Immunodeficiency Virus Type 1 (HIV-1) gp120-Specific Antibodies in Neonates Receiving an HIV-1 Recombinant gp120 Vaccine

Author

AIDS Clinical Trials Group 230 Collaborators, McFarland, Elizabeth J., Borkowsky, William, Fenton, Terry, Wara, Diane, McNamara, James, Samson, Pearl, Kang, Minhee, Mofenson, Lynne, Cunningham, Coleen, Duliege, Anne-Marie, Sinangil, Faruk, Spector, Stephen A., Jimenez, Eleanor, Bryson, Yvonne, Burchett, Sandra, Frenkel, Lisa M., Yogev, Ram, Gigliotti, Francis, Luzuriaga,, Katherine, and Livingston, Robert A.

Published
2001

24. Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved

Author

Wiehe, Kevin, Easterhoff, David, Luo, Kan, Nicely, Nathan I., Bradley, Todd, Jaeger, Frederick H., Dennison, Moses S., Zhang, Ruijun, Lloyd, Krissey E., Stolarchuk, Christina, Parks, Robert, Sutherland, Laura L., Scearce, Richard M., Morris, Lynn, Kaewkungwal, Jaranit, Nitayaphan, Sorachai, Pitisuttithum, Punnee, Rerks-Ngarm, Supachai, Sinangil, Faruk, Phogat, Sanjay, Michael, Nelson L., Kim, Jerome H., Kelsoe, Garnett, Montefiori, David C., Tomaras, Georgia D., Bonsignori, Mattia, Santra, Sampa, Kepler, Thomas B., Alam, Munir S., Moody, Anthony M., Liao, Hua-Xin, and Haynes, Barton F.

Published
2014
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25. Immune Responses to Human Immunodeficiency Virus (HIV) Type 1 Induced by Canarypox Expressing $HIV-1_mn$ gpl20, $HIV-1_SF2$ Recombinant gp120, or Both Vaccines in Seronegative Adults

Author

NIAID AIDS Vaccine Evaluation Group, Clements-Mann, Mary Lou, Weinhold, Kent, Matthews, Thomas J., Graham, Barney S., Gorse, Geoffrey J., Keefer, Michael C., McElrath, M. Juliana, Hsieh, Ray-Hahn, Mestecky, Jiri, Zolla-Pazner, Susan, Mascola, John, Schwartz, David, Siliciano, Robert, Corey, Lawrence, Wright, Peter F., Belshe, Robert, Dolin, Raphael, Jackson, Susan, Xu, Serena, Fast, Patricia, Walker, Mary Clare, Stablein, Don, Excler, Jean-Louis, Tartaglia, James, Duliege, Anne-Marie, Sinangil, Faruk, and Paoletti, Enzo

Published
1998

28. IFNL4genotype influences the rate of HIV-1 seroconversion in men who have sex with men

Author

Meza, Giovanna, Galián, Fátima, Jaimes-Bernal, Claudia, Márquez, Francisco J., Sinangil, Faruk, Scagnolari, Carolina, Real, Luis Miguel, Forthal, Donald, and Caruz, Antonio

Abstract

ABSTRACTIndividuals lacking interferon lambda 4 (IFNL4) protein due to a common null mutation (rs368234815) in the IFNL4gene display higher resistance against several infections. The influence of IFNL4 on HIV-1 infection is still under discussion and conflicting results have been reported. This study intended to corroborate or refute the association of the null allele of IFNL4and HIV-1 predisposition in a cohort of men who have sex with men (MSM). IFNL4null genotype was assessed on 619 HIV-1-seronegative MSM who were followed for 36 months during a trial of a prophylactic vaccine against HIV-1. Of those, 257 individuals seroconverted during this period. A logistic regression model was constructed including demographic and IFNL4genotype. In addition, a meta-analysis using data from the current study and other European populations was conducted. The null IFNL4genotypes were correlated with lower HIV-1 seroconversion (Adjusted OR = 0.4 [95%CI: 0.2–0.8], P = 0.008) and longer time to seroconversion (889 vs. 938 days, P= 0.01). These results were validated by a meta-analysis incorporating data from other European populations and the result yielded a significant association of the IFNL4null genotype under a dominant model with a lower probability of HIV-1 infection (OR=0.4 [95% CI: 0.3-0.6]; P= 1.3 x 10E-5).

Published
2022
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29. Vaccine Induction of Antibodies against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2

Author

Liao, Hua-Xin, Bonsignori, Mattia, Alam, Munir S., McLellan, Jason S., Tomaras, Georgia D., Moody, Anthony M., Kozink, Daniel M., Hwang, Kwan-Ki, Chen, Xi, Tsao, Chun-Yen, Liu, Pinghuang, Lu, Xiaozhi, Parks, Robert J., Montefiori, David C., Ferrari, Guido, Pollara, Justin, Rao, Mangala, Peachman, Kristina K., Santra, Sampa, Letvin, Norman L., Karasavvas, Nicos, Yang, Zhi-Yong, Dai, Kaifan, Pancera, Marie, Gorman, Jason, Wiehe, Kevin, Nicely, Nathan I., Rerks-Ngarm, Supachai, Nitayaphan, Sorachai, Kaewkungwal, Jaranit, Pitisuttithum, Punnee, Tartaglia, James, Sinangil, Faruk, Kim, Jerome H., Michael, Nelson L., Kepler, Thomas B., Kwong, Peter D., Mascola, John R., Nabel, Gary J., Pinter, Abraham, Zolla-Pazner, Susan, and Haynes, Barton F.

Published
2013
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31. Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial

Author

Pitisuttithum, Punnee, primary, Nitayaphan, Sorachai, additional, Chariyalertsak, Suwat, additional, Kaewkungwal, Jaranit, additional, Dawson, Peter, additional, Dhitavat, Jittima, additional, Phonrat, Benjaluck, additional, Akapirat, Siriwat, additional, Karasavvas, Nicos, additional, Wieczorek, Lindsay, additional, Polonis, Victoria, additional, Eller, Michael A, additional, Pegu, Poonam, additional, Kim, Dohoon, additional, Schuetz, Alexandra, additional, Jongrakthaitae, Surat, additional, Zhou, Yingjun, additional, Sinangil, Faruk, additional, Phogat, Sanjay, additional, Diazgranados, Carlos A, additional, Tartaglia, James, additional, Heger, Elizabeth, additional, Smith, Kirsten, additional, Michael, Nelson L, additional, Excler, Jean-Louis, additional, Robb, Merlin L, additional, Kim, Jerome H, additional, O'Connell, Robert J, additional, Vasan, Sandhya, additional, Pitisuthitham, Arom, additional, Sabmee, Yupa, additional, Sirisopana, Narongrid, additional, Eamsila, Chirapa, additional, Savaraj, Prapaporn, additional, Labwech, Wanlaya, additional, Teerachia, Siriluck, additional, Chotirosniramit, Nuntisa, additional, Supindham, Taweewat, additional, Pruenglampoo, Boonlure, additional, Sugandhavesa, Patcharaphan, additional, Kosashunhanan, Natthapol, additional, Kaewthip, Oranitcha, additional, Sroysuwan, Piyathida, additional, Jarujareet, Pawinee, additional, Ratto-Kim, Silvia, additional, Molnar, Sebastian, additional, Schoen, Jesse, additional, Churikanont, Nampueng, additional, Getchalarat, Saowanit, additional, Sangnoi, Nongluck, additional, Nuntapinit, Bessara, additional, Phramtong, Anant, additional, Grandin, Pornsuk V., additional, Madnote, Sirinan, additional, Rittiroongrad, Surawach, additional, Kaewboon, Boot, additional, Trichavaroj, Rapee, additional, Puangkaew, Jiraporn, additional, Chantakulkij, Somsak, additional, Rakyat, Phiromrat, additional, Panjapornsuk, Pornchanok, additional, Tragonlugsana, Nipattra, additional, Chuenarom, Weerawan, additional, de Souza, Mark, additional, Ngauy, Viseth, additional, Phanuphak, Nittaya, additional, Chomchey, Nitiya, additional, Saengtawan, Puttachard, additional, Teeratakulpisarn, Nipat, additional, Rerknimitr, Rungsun, additional, Kroon, Eugene, additional, Lee, Carter A., additional, and Chinaworapong, Suchada, additional

Published
2020
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32. Boosting with AIDSVAX B/E Enhances Env Constant Region 1 and 2 Antibody-Dependent Cellular Cytotoxicity Breadth and Potency

Author

Easterhoff, David, primary, Pollara, Justin, additional, Luo, Kan, additional, Tolbert, William D., additional, Young, Brianna, additional, Mielke, Dieter, additional, Jha, Shalini, additional, O’Connell, Robert J., additional, Vasan, Sandhya, additional, Kim, Jerome, additional, Michael, Nelson L., additional, Excler, Jean-Louis, additional, Robb, Merlin L., additional, Rerks-Ngarm, Supachai, additional, Kaewkungwal, Jaranit, additional, Pitisuttithum, Punnee, additional, Nitayaphan, Sorachai, additional, Sinangil, Faruk, additional, Tartaglia, James, additional, Phogat, Sanjay, additional, Kepler, Thomas B., additional, Alam, S. Munir, additional, Wiehe, Kevin, additional, Saunders, Kevin O., additional, Montefiori, David C., additional, Tomaras, Georgia D., additional, Moody, M. Anthony, additional, Pazgier, Marzena, additional, Haynes, Barton F., additional, and Ferrari, Guido, additional

Published
2020
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33. HIV vaccine delayed boosting increases Env variable region 2–specific antibody effector functions

Author

Easterhoff, David, primary, Pollara, Justin, additional, Luo, Kan, additional, Janus, Benjamin, additional, Gohain, Neelakshi, additional, Williams, LaTonya D., additional, Tay, Matthew Zirui, additional, Monroe, Anthony, additional, Peachman, Kristina, additional, Choe, Misook, additional, Min, Susie, additional, Lusso, Paolo, additional, Zhang, Peng, additional, Go, Eden P., additional, Desaire, Heather, additional, Bonsignori, Mattia, additional, Hwang, Kwan-Ki, additional, Beck, Charles, additional, Kakalis, Matina, additional, O’Connell, Robert J., additional, Vasan, Sandhya, additional, Kim, Jerome H., additional, Michael, Nelson L., additional, Excler, Jean-Louis, additional, Robb, Merlin L., additional, Rerks-Ngarm, Supachai, additional, Kaewkungwal, Jaranit, additional, Pitisuttithum, Punnee, additional, Nitayaphan, Sorachai, additional, Sinangil, Faruk, additional, Tartaglia, James, additional, Phogat, Sanjay, additional, Wiehe, Kevin, additional, Saunders, Kevin O., additional, Montefiori, David C., additional, Tomaras, Georgia D., additional, Moody, M. Anthony, additional, Arthos, James, additional, Rao, Mangala, additional, Joyce, M. Gordon, additional, Ofek, Gilad A., additional, Ferrari, Guido, additional, and Haynes, Barton F., additional

Published
2020
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35. Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by immunization

Author

Lubeck, Michael D., Natuk, Robert, Myagkikh, Maria, Kalyan, Narender, Aldrich, Kristine, Sinangil, Faruk, Alipanah, Shabnam, Murthy, Shri C.S., Chanda, Pranab K., Nigida, Jr., Stephen M., Markham, Phillip D., Zolla-pazner, Susan, Steimer, Kathy, Wade, Mark, Reitz, Jr., Marvin S., Arthur, Larry O., Mizutani, Satoshi, Davis, Alan, Hung, Paul P., Gallo, Robert C., Eichberg, Jorg, and Robert-Guroff, Marjorie

Published
1997
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37. Human Immunodeficiency Virus Type 1 (HIV-1) gp120--Specific Antibodies in Neonates Receiving an HIV-1 Recombinant gp120 Vaccine. (Concise Communication)

Author

McFarland, Elizabeth J., Borkowsky, William, Fenton, Terry, Wara, Diane, McNamara, James, Samson, Pearl, Kang, Minhee, Mofenson, Lynne, Cunningham, Coleen, Duliege, Anne-Marie, Sinangil, Faruk, Spector, Stephen A., Jimenez, Eleanor, Bryson, Yvonne, Burchett, Sandra, Frenkel, Lisa M., Yogev, Ram, Gigliotti, Francis, Luzuriaga, Katherine, and Livingston, Robert A.

Subjects
HIV infection in children -- Physiological aspects, Infants (Newborn), Antibodies -- Measurement, Health
Published
2001

38. Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa

Author

Gray, Glenda E., primary, Huang, Ying, additional, Grunenberg, Nicole, additional, Laher, Fatima, additional, Roux, Surita, additional, Andersen-Nissen, Erica, additional, De Rosa, Stephen C., additional, Flach, Britta, additional, Randhawa, April K., additional, Jensen, Ryan, additional, Swann, Edith M., additional, Bekker, Linda-Gail, additional, Innes, Craig, additional, Lazarus, Erica, additional, Morris, Lynn, additional, Mkhize, Nonhlanhla N., additional, Ferrari, Guido, additional, Montefiori, David C., additional, Shen, Xiaoying, additional, Sawant, Sheetal, additional, Yates, Nicole, additional, Hural, John, additional, Isaacs, Abby, additional, Phogat, Sanjay, additional, DiazGranados, Carlos A., additional, Lee, Carter, additional, Sinangil, Faruk, additional, Michael, Nelson L., additional, Robb, Merlin L., additional, Kublin, James G., additional, Gilbert, Peter B., additional, McElrath, M. Juliana, additional, Tomaras, Georgia D., additional, and Corey, Lawrence, additional

Published
2019
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39. Boosting with ALVAC-HIV and AIDSVAX B/E enhances Env constant region 1 and 2 antibody-dependent cellular cytotoxicity

Author

Easterhoff, David, primary, Pollara, Justin, additional, Luo, Kan, additional, Tolbert, William D., additional, Young, Brianna, additional, Mielke, Dieter, additional, Jha, Shalini, additional, O’Connell, Robert J., additional, Vasan, Sandhya, additional, Kim, Jerome, additional, Michael, Nelson L., additional, Excler, Jean-Louis, additional, Robb, Merlin L., additional, Rerks-Ngarm, Supachai, additional, Kaewkungwal, Jaranit, additional, Pitisuttithum, Punnee, additional, Nitayaphan, Sorachai, additional, Sinangil, Faruk, additional, Tartaglia, James, additional, Phogat, Sanjay, additional, Kepler, Thomas B., additional, Alam, S. Munir, additional, Wiehe, Kevin, additional, Saunders, Kevin O., additional, Montefiori, David C., additional, Tomaras, Georgia D., additional, Moody, M. Anthony, additional, Pazgier, Marzena, additional, Haynes, Barton F., additional, and Ferrari, Guido, additional

Published
2019
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40. Late Boosting of the RV144 Regimen Improves the Magnitude and Quality of Immune Responses

Author

Pitisuttithum, Punnee, primary, Nitayapha, Sorachai, additional, Chariyalertsak, Suwat, additional, Kaewkungwal, Jaranit, additional, Dawson, Peter, additional, Dhitavat, Jittima, additional, Phonrat, Benjaluck, additional, Akapirat, Siriwat, additional, Karasavvas, Nicos, additional, Wieczorek, Lindsay, additional, Polonis, Victoria, additional, Eller, Michael A., additional, Pegu, Poonam, additional, Kim, Dohoon, additional, Schuetz, Alexandra, additional, Jongrakthaitae, Surat, additional, Zhou, Yingjun, additional, Sinangil, Faruk, additional, Phogat, Sanjay, additional, DiazGranados, Carlos A., additional, Tartaglia, James, additional, Heger, Elizabeth, additional, Smith, Kirsten, additional, Michael, Nelson L., additional, Excler, Jean-Louis, additional, Robb, Merlin L., additional, Kim, Jerome H., additional, O’Connell, Robert J., additional, and Vasan, Sandhya, additional

Published
2019
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41. Ethnic differences in the adaptation rate of HIV gp120 from a vaccine trial

Author

Berman Phillip W, Sinangil Faruk, Jobes David V, Arenas Miguel, Posada David, Pérez-Losada Marcos, and Crandall Keith A

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Differences in HIV-1 gp120 sequence variation were examined in North American volunteers who became infected during a phase III vaccine trial using the rgp120 vaccine. Molecular adaptation of the virus in vaccine and placebo recipients from different ethnic subgroups was compared by estimating the dN/dS ratios in viruses sampled from each individual using three different methods. ANOVA analyses detected significant differences in dN/dS ratios among races (P < 0.02). gp120 sequences from the black individuals showed higher mean dN/dS ratios for all estimators (1.24–1.45) than in other races (0.66–1.35), and several pairwise comparisons involving blacks remained significant (P < 0.05) after correction for multiple tests. In addition, black-placebo individuals showed significantly (P < 0.02) higher mean dN/dS ratios (1.3–1.66) than placebo individuals from the other races (0.65–1.56). These results suggest intrinsic differences among races in immune response and highlight the need for including multiple ethnicities in the design of future HIV-1 vaccine studies and trials.

Published
2009
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43. Functional Antibody Response Against V1V2 and V3 of HIV gp120 in the VAX003 and VAX004 Vaccine Trials

Author

Balasubramanian, Preetha, primary, Williams, Constance, additional, Shapiro, Mariya B., additional, Sinangil, Faruk, additional, Higgins, Keith, additional, Nádas, Arthur, additional, Totrov, Maxim, additional, Kong, Xiang-Peng, additional, Fiore-Gartland, Andrew J., additional, Haigwood, Nancy L., additional, Zolla-Pazner, Susan, additional, and Hioe, Catarina E., additional

Published
2018
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47. V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144

Author

Perez, Lautaro G., primary, Martinez, David R., additional, deCamp, Allan C., additional, Pinter, Abraham, additional, Berman, Phillip W., additional, Francis, Donald, additional, Sinangil, Faruk, additional, Lee, Carter, additional, Greene, Kelli, additional, Gao, Hongmei, additional, Nitayaphan, Sorachai, additional, Rerks-Ngarm, Supachai, additional, Kaewkungwal, Jaranit, additional, Pitisuttithum, Punnee, additional, Tartaglia, James, additional, O’Connell, Robert J., additional, Robb, Merlin L., additional, Michael, Nelson L., additional, Kim, Jerome H., additional, Gilbert, Peter, additional, and Montefiori, David C., additional

Published
2017
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48. Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women

Author

Gilbert, Peter B., primary, Excler, Jean-Louis, additional, Tomaras, Georgia D., additional, Carpp, Lindsay N., additional, Haynes, Barton F., additional, Liao, Hua-Xin, additional, Montefiori, David C., additional, Rerks-Ngarm, Supachai, additional, Pitisuttithum, Punnee, additional, Nitayaphan, Sorachai, additional, Kaewkungwal, Jaranit, additional, Kijak, Gustavo H., additional, Tovanabutra, Sodsai, additional, Francis, Donald P., additional, Lee, Carter, additional, Sinangil, Faruk, additional, Berman, Phillip W., additional, Premsri, Nakorn, additional, Kunasol, Prayura, additional, O’Connell, Robert J., additional, Michael, Nelson L., additional, Robb, Merlin L., additional, Morrow, Rhoda, additional, Corey, Lawrence, additional, and Kim, Jerome H., additional

Published
2017
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49. Comparison of Antibody Responses Induced by RV144, VAX003, and VAX004 Vaccination Regimens

Author

Karnasuta, Chitraporn, primary, Akapirat, Siriwat, additional, Madnote, Sirinan, additional, Savadsuk, Hathairat, additional, Puangkaew, Jiraporn, additional, Rittiroongrad, Surawach, additional, Rerks-Ngarm, Supachai, additional, Nitayaphan, Sorachai, additional, Pitisuttithum, Punnee, additional, Kaewkungwal, Jaranit, additional, Tartaglia, James, additional, Sinangil, Faruk, additional, Francis, Donald P., additional, Robb, Merlin L., additional, de Souza, Mark S., additional, Michael, Nelson L., additional, Excler, Jean-Louis, additional, Kim, Jerome H., additional, O'Connell, Robert J., additional, and Karasavvas, Nicos, additional

Published
2017
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50. P-C16 Differential Induction of Anti-V3 Crown Antibodies with Cradle and Ladle-Binding Modes in Response to HIV-1 Envelope Vaccination

Author

Kumar, Rajnish, primary, Williams, Constance, additional, Itri, Vincenza, additional, Wang, Shixia, additional, Lu, Shan, additional, Hessell, Ann, additional, Higgins, Keith, additional, Liu, Lily, additional, Haigwood, Nancy, additional, Sinangil, Faruk, additional, Gorny, Miroslaw, additional, Totrov, Max, additional, Kong, Xiang, additional, Nadas, Arthur, additional, Zolla-Pazner, Susan, additional, Hioe, Catarina, additional, and Balasubramanian, Preetha, additional

Published
2017
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