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1. Differences in neutralizing antibody sensitivities and envelope characteristics indicate distinct antigenic properties of Nigerian HIV-1 subtype G and CRF02_AG

Author

Wieczorek, Lindsay, Chang, David, Sanders-Buell, Eric, Zemil, Michelle, Martinez, Elizabeth, Schoen, Jesse, Chenine, Agnes-Laurence, Molnar, Sebastian, Barrows, Brittani, Poltavee, Kultida, Charurat, Man E., Abimiku, Alash’le, Blattner, William, Iroezindu, Michael, Kokogho, Afoke, Michael, Nelson L., Crowell, Trevor A., Ake, Julie A., Tovanabutra, Sodsai, and Polonis, Victoria R.

Published
2024
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2. Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

Author

Sankhala, Rajeshwer S., Lal, Kerri G., Jensen, Jaime L., Dussupt, Vincent, Mendez-Rivera, Letzibeth, Bai, Hongjun, Wieczorek, Lindsay, Mayer, Sandra V., Zemil, Michelle, Wagner, Danielle A., Townsley, Samantha M., Hajduczki, Agnes, Chang, William C., Chen, Wei-Hung, Donofrio, Gina C., Jian, Ningbo, King, Hannah A. D., Lorang, Cynthia G., Martinez, Elizabeth J., Rees, Phyllis A., Peterson, Caroline E., Schmidt, Fabian, Hart, Tricia J., Duso, Debra K., Kummer, Lawrence W., Casey, Sean P., Williams, Jazmean K., Kannan, Shruthi, Slike, Bonnie M., Smith, Lauren, Swafford, Isabella, Thomas, Paul V., Tran, Ursula, Currier, Jeffrey R., Bolton, Diane L., Davidson, Edgar, Doranz, Benjamin J., Hatziioannou, Theodora, Bieniasz, Paul D., Paquin-Proulx, Dominic, Reiley, William W., Rolland, Morgane, Sullivan, Nancy J., Vasan, Sandhya, Collins, Natalie D., Modjarrad, Kayvon, Gromowski, Gregory D., Polonis, Victoria R., Michael, Nelson L., Krebs, Shelly J., and Joyce, M. Gordon

Published
2024
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3. Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity

Author

Chen, Wei-Hung, Hajduczki, Agnes, Martinez, Elizabeth J., Bai, Hongjun, Matz, Hanover, Hill, Thomas M., Lewitus, Eric, Chang, William C., Dawit, Layla, Peterson, Caroline E., Rees, Phyllis A., Ajayi, Adelola B., Golub, Emily S., Swafford, Isabella, Dussupt, Vincent, David, Sapna, Mayer, Sandra V., Soman, Sandrine, Kuklis, Caitlin, Corbitt, Courtney, King, Jocelyn, Choe, Misook, Sankhala, Rajeshwer S., Thomas, Paul V., Zemil, Michelle, Wieczorek, Lindsay, Hart, Tricia, Duso, Debora, Kummer, Larry, Yan, Lianying, Sterling, Spencer L., Laing, Eric D., Broder, Christopher C., Williams, Jazmean K., Davidson, Edgar, Doranz, Benjamin J., Krebs, Shelly J., Polonis, Victoria R., Paquin-Proulx, Dominic, Rolland, Morgane, Reiley, William W., Gromowski, Gregory D., Modjarrad, Kayvon, Dooley, Helen, and Joyce, M. Gordon

Published
2023
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4. Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study

Author

Marichannegowda, Manukumar Honnayakanahalli, Zemil, Michelle, Wieczorek, Lindsay, Sanders-Buell, Eric, Bose, Meera, O'Sullivan, Anne Marie, King, David, Francisco, Leilani, Diaz-Mendez, Felisa, Setua, Saini, Chomont, Nicolas, Phanuphak, Nittaya, Ananworanich, Jintanat, Hsu, Denise, Vasan, Sandhya, Michael, Nelson L., Eller, Leigh Anne, Tovanabutra, Sodsai, Tagaya, Yutaka, Robb, Merlin L., Polonis, Victoria R., and Song, Hongshuo

Published
2023
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5. Contemporary HIV-1 consensus Env with AI-assisted redesigned hypervariable loops promote antibody binding

Author

Bai, Hongjun, primary, Lewitus, Eric, additional, Li, Yifan, additional, Thomas, Paul V., additional, Zemil, Michelle, additional, Merbah, Mélanie, additional, Peterson, Caroline E., additional, Thuraisamy, Thujitha, additional, Rees, Phyllis A., additional, Hajduczki, Agnes, additional, Dussupt, Vincent, additional, Slike, Bonnie, additional, Mendez-Rivera, Letzibeth, additional, Schmid, Annika, additional, Kavusak, Erin, additional, Rao, Mekhala, additional, Smith, Gabriel, additional, Frey, Jessica, additional, Sims, Alicea, additional, Wieczorek, Lindsay, additional, Polonis, Victoria, additional, Krebs, Shelly J., additional, Ake, Julie A., additional, Vasan, Sandhya, additional, Bolton, Diane L., additional, Joyce, M. Gordon, additional, Townsley, Samantha, additional, and Rolland, Morgane, additional

Published
2024
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6. 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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7. Extracellular vesicle isolation methods identify distinct HIV‐1 particles released from chronically infected T‐cells.

Author

Molnar, Sebastian M., Kim, Yuriy, Wieczorek, Lindsay, Williams, Anastasia, Patil, Kajal Ashok, Khatkar, Pooja, Santos, Mark F., Mensah, Gifty, Lorico, Aurelio, Polonis, Victoria R., and Kashanchi, Fatah

Subjects
EXTRACELLULAR vesicles, HIV, PARTICLE size distribution, VIRAL envelopes, PARTICLE analysis, T cells
Abstract

The current study analyzed the intersecting biophysical, biochemical, and functional properties of extracellular particles (EPs) with the human immunodeficiency virus type‐1 (HIV‐1) beyond the currently accepted size range for HIV‐1. We isolated five fractions (Frac‐A through Frac‐E) from HIV‐infected cells by sequential differential ultracentrifugation (DUC). All fractions showed a heterogeneous size distribution with median particle sizes greater than 100 nm for Frac‐A through Frac‐D but not for Frac‐E, which contained small EPs with an average size well below 50 nm. Synchronized and released cultures contained large infectious EPs in Frac‐A, with markers of amphisomes and viral components. Additionally, Frac‐E uniquely contained EPs positive for CD63, HSP70, and HIV‐1 proteins. Despite its small average size, Frac‐E contained membrane‐protected viral integrase, detectable only after SDS treatment, indicating that it is enclosed in vesicles. Single particle analysis with dSTORM further supported these findings as CD63, HIV‐1 integrase, and the viral surface envelope (Env) glycoprotein (gp) colocalized on the same Frac‐E particles. Surprisingly, Frac‐E EPs were infectious, and infectivity was significantly reduced by immunodepleting Frac‐E with anti‐CD63, indicating the presence of this protein on the surface of infectious small EPs in Frac‐E. To our knowledge, this is the first time that extracellular vesicle (EV) isolation methods have identified infectious small HIV‐1 particles (smHIV‐1) that are under 50 nm. Collectively, our data indicate that the crossroads between EPs and HIV‐1 potentially extend beyond the currently accepted biophysical properties of HIV‐1, which may have further implications for viral pathogenesis. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States

Author

Wieczorek, Lindsay, primary, Sanders-Buell, Eric, additional, Zemil, Michelle, additional, Lewitus, Eric, additional, Kavusak, Erin, additional, Heller, Jonah, additional, Molnar, Sebastian, additional, Rao, Mekhala, additional, Smith, Gabriel, additional, Bose, Meera, additional, Nguyen, Amy, additional, Dhungana, Adwitiya, additional, Okada, Katherine, additional, Parisi, Kelly, additional, Silas, Daniel, additional, Slike, Bonnie, additional, Ganesan, Anuradha, additional, Okulicz, Jason, additional, Lalani, Tahaniyat, additional, Agan, Brian K., additional, Crowell, Trevor A., additional, Darden, Janice, additional, Rolland, Morgane, additional, Vasan, Sandhya, additional, Ake, Julie, additional, Krebs, Shelly J., additional, Peel, Sheila, additional, Tovanabutra, Sodsai, additional, and Polonis, Victoria R., additional

Published
2023
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9. Safety and immunogenicity of Ad26 and MVA vaccines in acutely treated HIV and effect on viral rebound after antiretroviral therapy interruption

Author

Colby, Donn J., Sarnecki, Michal, Barouch, Dan H., Tipsuk, Somporn, Stieh, Daniel J., Kroon, Eugène, Schuetz, Alexandra, Intasan, Jintana, Sacdalan, Carlo, Pinyakorn, Suteeraporn, Grandin, Pornsuk, Song, Hongshuo, Tovanabutra, Sodsai, Shubin, Zhanna, Kim, Dohoon, Paquin-Proulx, Dominic, Eller, Michael A., Thomas, Rasmi, de Souza, Mark, Wieczorek, Lindsay, Polonis, Victoria R., Pagliuzza, Amélie, Chomont, Nicolas, Peter, Lauren, Nkolola, Joseph P., Vingerhoets, Johan, Truyers, Carla, Pau, Maria G., Schuitemaker, Hanneke, Phanuphak, Nittaya, Michael, Nelson, Robb, Merlin L., Tomaka, Frank L., and Ananworanich, Jintanat

Published
2020
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10. 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

11. Chemically modified peptides based on the membrane-proximal external region of the HIV-1 envelope induce high-titer, epitope-specific nonneutralizing antibodies in rabbits.

Author

Venditto, Vincent J, Wieczorek, Lindsay, Molnar, Sebastian, Teque, Fernando, Landucci, Gary, Watson, Douglas S, Forthal, Donald, Polonis, Victoria R, Levy, Jay A, and Szoka, Francis C, Jr

Subjects
AIDS Vaccines: chemistry, immunology, Animals, Antibodies, Monoclonal: immunology, Antibodies, Neutralizing: immunology, Antibody Affinity: immunology, Cell Line, Chromatography, Affinity, Cross Reactions: immunology, Epitopes: chemistry, immunology, HIV Antibodies: immunology, HIV Envelope Protein gp41: chemistry, immunology, HIV-1: immunology, Neutralization Tests, Rabbits, env Gene Products, Human Immunodeficiency Virus: immunology
Abstract

Broadly neutralizing monoclonal antibodies (bNAbs) 2F5 and 4E10 bind to the membrane proximal external region (MPER) of gp41 and also cross-react with phospholipids. In this study, we investigated if chemical modifications on the MPER adjacent to 2F5 and 4E10 epitopes using mimetics of inflammation-associated posttranslational modifications to induce 2F5- and 4E10-like bNAbs can break tolerance. We synthesized a series of chemically modified peptides spanning the MPER. The serine, threonine, and tyrosine residues in the peptides were modified with sulfate, phosphate, or nitrate moieties and presented in liposomes for rabbit immunizations. All immunizations resulted in high antisera titers directed toward both the modified and unmodified immunogens. Tyrosine modification was observed to significantly suppress antiepitope responses. Sera with strong anti-gp140 titers were purified by affinity chromatography toward the MPER peptide and found to possess a higher affinity toward the MPER than did the bNAbs 2F5 and 4E10. Modest neutralization was observed in the H9 neutralization assay, but neutralization was not observed in the TZM-bl cell or peripheral blood mononuclear cell (PBMC) neutralization assay platforms. Although neutralizing antibodies were not induced by this approach, we conclude that chemical modifications can increase the immune responses to poorly immunogenic antigens, suggesting that chemical modification in an appropriate immunization protocol should be explored further as an HIV-1 vaccine strategy.

Published
2014

12. 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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13. Anti-HIV antibody development up to 1 year after antiretroviral therapy initiation in acute HIV infection

Author

Mitchell, Julie L., Pollara, Justin, Dietze, Kenneth, Edwards, R. Whitney, Nohara, Junsuke, N'guessan, Kombo F., Zemil, Michelle, Buranapraditkun, Supranee, Takata, Hiroshi, Li, Yifan, Muir, Roshell, Kroon, Eugene, Pinyakorn, Suteeraporn, Jha, Shalini, Manasnayakorn, Sopark, Chottanapund, Suthat, Thantiworasit, Pattarawat, Prueksakaew, Peeriya, Ratnaratorn, Nisakorn, Nuntapinit, Bessara, Fox, Lawrence, Tovanabutra, Sodsai, Paquin-Proulx, Dominic, Wieczorek, Lindsay, Polonis, Victoria R., Maldarelli, Frank, Haddad, Elias K., Phanuphak, Praphan, Sacdalan, Carlo P., Rolland, Morgane, Phanuphak, Nittaya, Ananworanich, Jintanat, Vasan, Sandhya, Ferrari, Guido, and Trautmann, Lydie

Subjects
HIV antibodies -- Identification and classification, Immune response -- Observations, Antiviral agents -- Patient outcomes, HIV infection -- Development and progression -- Drug therapy, Health care industry
Abstract

Early initiation of antiretroviral therapy (ART) in acute HIV infection (AHI) is effective at limiting seeding of the HIV viral reservoir, but little is known about how the resultant decreased antigen load affects long-term Ab development after ART. We report here that Env-specific plasma antibody (Ab) levels and Ab-dependent cellular cytotoxicity (ADCC) increased during the first 24 weeks of ART and correlated with Ab levels persisting after 48 weeks of ART. Participants treated in AHI stage 1 had lower Env-specific Ab levels and ADCC activity on ART than did those treated later. Importantly, participants who initiated ART after peak viremia in AHI developed elevated cross-clade ADCC responses that were detectable 1 year after ART initiation, even though clinically undetectable viremia was reached by 24 weeks. These data suggest that there is more germinal center (GC) activity in the later stages of AHI and that Ab development continues in the absence of detectable viremia during the first year of suppressive ART. The development of therapeutic interventions that can enhance earlier development of GCs in AHI and Abs after ART initiation could provide important protection against the viral reservoir that is seeded in individuals treated early in the disease., Introduction Initiation of antiretroviral therapy (ART) during acute HIV infection (AHI) is associated with multiple benefits, including decreased HIV reservoir size (1-6) and preservation of a homogenous viral reservoir with [...]

Published
2022
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14. Targeting the Spike Receptor Binding Domain Class V Cryptic Epitope by an Antibody with Pan-Sarbecovirus Activity

Author

Jensen, Jaime L., primary, Sankhala, Rajeshwer S., additional, Dussupt, Vincent, additional, Bai, Hongjun, additional, Hajduczki, Agnes, additional, Lal, Kerri G., additional, Chang, William C., additional, Martinez, Elizabeth J., additional, Peterson, Caroline E., additional, Golub, Emily S., additional, Rees, Phyllis A., additional, Mendez-Rivera, Letzibeth, additional, Zemil, Michelle, additional, Kavusak, Erin, additional, Mayer, Sandra V., additional, Wieczorek, Lindsay, additional, Kannan, Shruthi, additional, Doranz, Benjamin J., additional, Davidson, Edgar, additional, Yang, Eun Sung, additional, Zhang, Yi, additional, Chen, Man, additional, Choe, Misook, additional, Wang, Lingshu, additional, Gromowski, Gregory D., additional, Koup, Richard A., additional, Michael, Nelson L., additional, Polonis, Victoria R., additional, Rolland, Morgane, additional, Modjarrad, Kayvon, additional, Krebs, Shelly J., additional, and Joyce, M. Gordon, additional

Published
2023
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15. 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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16. Convalescent human IgG, but not IgM, from COVID-19 survivors confers dose-dependent protection against SARS-CoV-2 replication and disease in hamsters

Author

King, Hannah A. D., primary, Dussupt, Vincent, additional, Mendez-Rivera, Letzibeth, additional, Slike, Bonnie M., additional, Tran, Ursula, additional, Jackson, Nathan D., additional, Barkei, Erica, additional, Zemil, Michelle, additional, Tourtellott-Fogt, Emily, additional, Kuklis, Caitlin H., additional, Soman, Sandrine, additional, Ahmed, Aslaa, additional, Porto, Maciel, additional, Kitajewski, Christopher, additional, Spence, Brittany, additional, Benetiene, Dalia, additional, Wieczorek, Lindsay, additional, Kar, Swagata, additional, Gromowski, Gregory, additional, Polonis, Victoria R., additional, Krebs, Shelly J., additional, Modjarrad, Kayvon, additional, and Bolton, Diane L., additional

Published
2023
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17. Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

Author

Kuriakose Gift, Syna, primary, Wieczorek, Lindsay, additional, Sanders-Buell, Eric, additional, Zemil, Michelle, additional, Molnar, Sebastian, additional, Donofrio, Gina, additional, Townsley, Samantha, additional, Chenine, Agnes L., additional, Bose, Meera, additional, Trinh, Hung V., additional, Barrows, Brittani M., additional, Sriplienchan, Somchai, additional, Kitsiripornchai, Suchai, additional, Nitayapan, Sorachai, additional, Eller, Leigh-Anne, additional, Rao, Mangala, additional, Ferrari, Guido, additional, Michael, Nelson L., additional, Ake, Julie A., additional, Krebs, Shelly J., additional, Robb, Merlin L., additional, Tovanabutra, Sodsai, additional, and Polonis, Victoria R., additional

Published
2023
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18. Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission

Author

Barrows, Brittani M., primary, Krebs, Shelly J., additional, Jian, Ningbo, additional, Zemil, Michelle, additional, Slike, Bonnie M., additional, Dussupt, Vincent, additional, Tran, Ursula, additional, Mendez-Rivera, Letzibeth, additional, Chang, David, additional, O’Sullivan, Anne Marie, additional, Mann, Brendan, additional, Sanders-Buell, Eric, additional, Shubin, Zhanna, additional, Creegan, Matt, additional, Paquin-Proulx, Dominic, additional, Ehrenberg, Philip, additional, Laurence-Chenine, Agnes, additional, Srithanaviboonchai, Kriengkrai, additional, Thomas, Rasmi, additional, Eller, Michael A., additional, Ferrari, Guido, additional, Robb, Merlin, additional, Rao, Venigalla, additional, Tovanabutra, Sodsai, additional, Polonis, Victoria R., additional, and Wieczorek, Lindsay, additional

Published
2022
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19. Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting

Author

Marichannegowda, Manukumar Honnayakanahalli, Zemil, Michelle, Wieczorek, Lindsay, Sanders-Buell, Eric, Bose, Meera, O’Sullivan, Anne Marie, King, David, Francisco, Leilani, Diaz-Mendez, Felisa, Setua, Saini, Chomont, Nicolas, Phanuphak, Nittaya, Ananworanich, Jintanat, Hsu, Denise, Vasan, Sandhya, Michael, Nelson L., Eller, Leigh Anne, Tovanabutra, Sodsai, Tagaya, Yutaka, Robb, Merlin L., Polonis, Victoria R., and Song, Hongshuo

Subjects
Article
Abstract

The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the underlying mechanisms remain unclear. The difficulty in capturing the earliest moment of coreceptor switchin vivolimits our understanding of this phenomenon. Here, by tracking the evolution of the transmitted/founder (T/F) HIV-1 in a prospective cohort of individuals at risk for HIV-1 infection identified very early in acute infection, we investigated this process with high resolution. The earliest X4 variants evolved from the R5 tropic T/F strains. Strong X4 usage can be conferred by a single mutation. The mutations responsible for coreceptor switch can confer escape to neutralization and drive X4 variants to replicate mainly in the central memory and naïve CD4+ T cells. We propose a novel concept to explain the co-evolution of virus antigenicity and entry tropism termed “escape by shifting”. This concept posits that for viruses with receptor or coreceptor flexibility, entry tropism alteration represents a mechanism of immune evasionin vivo.

Published
2023

20. Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection

Author

Wieczorek, Lindsay, primary, Zemil, Michelle, additional, Merbah, Mélanie, additional, Dussupt, Vincent, additional, Kavusak, Erin, additional, Molnar, Sebastian, additional, Heller, Jonah, additional, Beckman, Bradley, additional, Wollen-Roberts, Suzanne, additional, Peachman, Kristina K., additional, Darden, Janice M., additional, Krebs, Shelly, additional, Rolland, Morgane, additional, Peel, Sheila A., additional, and Polonis, Victoria R., additional

Published
2022
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21. Convalescent human IgG, but not IgM, from COVID-19 survivors confers dosedependent protection against SARS-CoV-2 replication and disease in hamsters.

Author

King, Hannah A. D., Dussupt, Vincent, Mendez-Rivera, Letzibeth, Slike, Bonnie M., Tran, Ursula, Jackson, Nathan D., Barkei, Erica, Zemil, Michelle, Tourtellott-Fogt, Emily, Kuklis, Caitlin H., Soman, Sandrine, Ahmed, Aslaa, Porto, Maciel, Kitajewski, Christopher, Spence, Brittany, Benetiene, Dalia, Wieczorek, Lindsay, Kar, Swagata, Gromowski, Gregory, and Polonis, Victoria R.

Subjects
CONVALESCENT plasma, IMMUNOGLOBULIN G, HAMSTERS, COVID-19 pandemic, GOLDEN hamster
Abstract

Introduction: Antibody therapeutic strategies have served an important role during the COVID-19 pandemic, even as their effectiveness has waned with the emergence of escape variants. Here we sought to determine the concentration of convalescent immunoglobulin required to protect against disease from SARSCoV- 2 in a Syrian golden hamster model. Methods: Total IgG and IgM were isolated from plasma of SARS-CoV-2 convalescent donors. Dose titrations of IgG and IgM were infused into hamsters 1 day prior to challenge with SARS-CoV-2 Wuhan-1. Results: The IgM preparation was found to have ~25-fold greater neutralization potency than IgG. IgG infusion protected hamsters from disease in a dosedependent manner, with detectable serum neutralizing titers correlating with protection. Despite a higher in vitro neutralizing potency, IgM failed to protect against disease when transferred into hamsters. Discussion: This study adds to the growing body of literature that demonstrates neutralizing IgG antibodies are important for protection from SARS-CoV-2 disease, and confirms that polyclonal IgG in sera can be an effective preventative strategy if the neutralizing titers are sufficiently high. In the context of new variants, against which existing vaccines or monoclonal antibodies have reduced efficacy, sera from individuals who have recovered from infection with the emerging variant may potentially remain an efficacious tool [ABSTRACT FROM AUTHOR]

Published
2023
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22. Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies.

Author

Gift, Syna Kuriakose, Wieczorek, Lindsay, Sanders-Buell, Eric, Zemil, Michelle, Molnar, Sebastian, Donofrio, Gina, Townsley, Samantha, Chenine, Agnes L., Bose, Meera, Trinh, Hung V., Barrows, Brittani M., Sriplienchan, Somchai, Kitsiripornchai, Suchai, Nitayapan, Sorachai, Eller, Leigh-Anne, Rao, Mangala, Ferrari, Guido, Michael, Nelson L., Ake, Julie A., and Krebs, Shelly J.

Subjects
*ANTIBODY formation, *HIV, *ANTIBODY-dependent cell cytotoxicity, *VIRAL load, *IMMUNOGLOBULINS, *IMMUNE response
Abstract

Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01_AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration [IC50] geometric mean titer [GMT] = 2,010 versus 184; P = 0.001) and 2 years (GMT = 3,479 versus 340; P = 0.015), compared to participants that developed ANAb responses after 6 months. Participants with later development of ANAb tended to develop an earlier, potent heterologous tier 1 (92TH023) neutralizing antibody (NAb) response (P = 0.049). CRF01_AE founder Env V1V2 loop lengths correlated indirectly with the timing (P = 0.002, r = 20.675) and directly with magnitude (P = 0.005, r = 0.635) of ANAb responses; Envs with longer V1V2 loop lengths elicited earlier and more potent ANAb responses. While ANAb responses did not associate with viral load, the viral load set point correlated directly with neutralization of the heterologous 92TH023 strain (P = 0.007, r = 0.638). In contrast, a striking inverse correlation was observed between viral load set point and peak ADCC against heterologous 92TH023 Env strain (P = 0.0005, r = 20.738). These data indicate that specific antibody functions can be differentially related to viral load set point and may affect HIV-1 pathogenesis. Exploiting Env properties, such as V1V2 length, could facilitate development of subtype-specific vaccines that elicit more effective immune responses and improved protection. IMPORTANCE Development of an effective HIV-1 vaccine will be facilitated by better understanding the dynamics between the founder virus and the early humoral responses. Variations between subtypes may influence the evolution of immune responses and should be considered as we strive to understand these dynamics. In this study, autologous founder envelope neutralization and heterologous functional humoral responses were evaluated after acute infection by HIV-1 CRF01_AE, a subtype that has not been thoroughly characterized. The evolution of these humoral responses was assessed in relation to envelope characteristics, magnitude of elicited immune responses, and viral load. Understanding immune parameters in natural infection will improve our understanding of protective responses and aid in the development of immunogens that elicit protective functional antibodies. Advancing our knowledge of correlates of positive clinical outcomes should lead to the design of more efficacious vaccines. [ABSTRACT FROM AUTHOR]

Published
2023
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23. SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity

Author

Joyce, M. Gordon, primary, Chen, Wei-Hung, additional, Sankhala, Rajeshwer S., additional, Hajduczki, Agnes, additional, Thomas, Paul V., additional, Choe, Misook, additional, Martinez, Elizabeth J., additional, Chang, William C., additional, Peterson, Caroline E., additional, Morrison, Elaine B., additional, Smith, Clayton, additional, Chen, Rita E., additional, Ahmed, Aslaa, additional, Wieczorek, Lindsay, additional, Anderson, Alexander, additional, Case, James Brett, additional, Li, Yifan, additional, Oertel, Therese, additional, Rosado, Lorean, additional, Ganesh, Akshaya, additional, Whalen, Connor, additional, Carmen, Joshua M., additional, Mendez-Rivera, Letzibeth, additional, Karch, Christopher P., additional, Gohain, Neelakshi, additional, Villar, Zuzana, additional, McCurdy, David, additional, Beck, Zoltan, additional, Kim, Jiae, additional, Shrivastava, Shikha, additional, Jobe, Ousman, additional, Dussupt, Vincent, additional, Molnar, Sebastian, additional, Tran, Ursula, additional, Kannadka, Chandrika B., additional, Soman, Sandrine, additional, Kuklis, Caitlin, additional, Zemil, Michelle, additional, Khanh, Htet, additional, Wu, Weimin, additional, Cole, Matthew A., additional, Duso, Debra K., additional, Kummer, Larry W., additional, Lang, Tricia J., additional, Muncil, Shania E., additional, Currier, Jeffrey R., additional, Krebs, Shelly J., additional, Polonis, Victoria R., additional, Rajan, Saravanan, additional, McTamney, Patrick M., additional, Esser, Mark T., additional, Reiley, William W., additional, Rolland, Morgane, additional, de Val, Natalia, additional, Diamond, Michael S., additional, Gromowski, Gregory D., additional, Matyas, Gary R., additional, Rao, Mangala, additional, Michael, Nelson L., additional, and Modjarrad, Kayvon, additional

Published
2021
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25. A SARS-CoV-2 spike ferritin nanoparticle vaccine protects hamsters against Alpha and Beta virus variant challenge

Author

Wuertz, Kathryn McGuckin, primary, Barkei, Erica K., additional, Chen, Wei-Hung, additional, Martinez, Elizabeth J., additional, Lakhal-Naouar, Ines, additional, Jagodzinski, Linda L., additional, Paquin-Proulx, Dominic, additional, Gromowski, Gregory D., additional, Swafford, Isabella, additional, Ganesh, Akshaya, additional, Dong, Ming, additional, Zeng, Xiankun, additional, Thomas, Paul V., additional, Sankhala, Rajeshwer S., additional, Hajduczki, Agnes, additional, Peterson, Caroline E., additional, Kuklis, Caitlin, additional, Soman, Sandrine, additional, Wieczorek, Lindsay, additional, Zemil, Michelle, additional, Anderson, Alexander, additional, Darden, Janice, additional, Hernandez, Heather, additional, Grove, Hannah, additional, Dussupt, Vincent, additional, Hack, Holly, additional, de la Barrera, Rafael, additional, Zarling, Stasya, additional, Wood, James F., additional, Froude, Jeffrey W., additional, Gagne, Matthew, additional, Henry, Amy R., additional, Mokhtari, Elham Bayat, additional, Mudvari, Prakriti, additional, Krebs, Shelly J., additional, Pekosz, Andrew S., additional, Currier, Jeffrey R., additional, Kar, Swagata, additional, Porto, Maciel, additional, Winn, Adrienne, additional, Radzyminski, Kamil, additional, Lewis, Mark G., additional, Vasan, Sandhya, additional, Suthar, Mehul, additional, Polonis, Victoria R., additional, Matyas, Gary R., additional, Boritz, Eli A., additional, Douek, Daniel C., additional, Seder, Robert A., additional, Daye, Sharon P., additional, Rao, Mangala, additional, Peel, Sheila A., additional, Joyce, M. Gordon, additional, Bolton, Diane L., additional, Michael, Nelson L., additional, and Modjarrad, Kayvon, additional

Published
2021
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27. Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge

Author

Om, Kier, primary, Paquin-Proulx, Dominic, additional, Montero, Maria, additional, Peachman, Kristina, additional, Shen, Xiaoying, additional, Wieczorek, Lindsay, additional, Beck, Zoltan, additional, Weiner, Joshua A., additional, Kim, Dohoon, additional, Li, Yifan, additional, Mdluli, Thembi, additional, Shubin, Zhanna, additional, Bryant, Christopher, additional, Sharma, Vishakha, additional, Tokarev, Andrey, additional, Dawson, Peter, additional, White, Yohann, additional, Appelbe, Oliver, additional, Klatt, Nichole R., additional, Tovanabutra, Sodsai, additional, Estes, Jacob D., additional, Matyas, Gary R., additional, Ferrari, Guido, additional, Alving, Carl R., additional, Tomaras, Georgia D., additional, Ackerman, Margaret E., additional, Michael, Nelson L., additional, Robb, Merlin L., additional, Polonis, Victoria, additional, Rolland, Morgane, additional, Eller, Michael A., additional, Rao, Mangala, additional, and Bolton, Diane L., additional

Published
2020
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28. Evaluation of HIV-1 neutralizing and binding antibodies in maternal-infant transmission in Thailand

Author

Wieczorek, Lindsay, primary, Peachman, Kristina, additional, Adams, Daniel J., additional, Barrows, Brittani, additional, Molnar, Sebastian, additional, Schoen, Jesse, additional, Dawson, Peter, additional, Bryant, Chris, additional, Chenine, Agnès-Laurence, additional, Sanders-Buell, Eric, additional, Srithanaviboonchai, Kriengkrai, additional, Pathipvanich, Panita, additional, Michael, Nelson L., additional, Robb, Merlin L., additional, Tovanabutra, Sodsai, additional, Rao, Mangala, additional, and Polonis, Victoria R., additional

Published
2020
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29. Novel monoclonal antibodies to the SERINC5 HIV-1 restriction factor detect endogenous and virion-associated SERINC5

Author

Molnar, Sebastian, primary, Wieczorek, Lindsay, additional, Zemil, Michelle, additional, Schulte, Bianca, additional, Martinez, Elizabeth, additional, Gift, Syna, additional, Tang, Lan, additional, Streeck, Hendrik, additional, Gramzinski, Robert A., additional, Michael, Nelson L., additional, Joyce, Gordon, additional, and Polonis, Victoria R., additional

Published
2020
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32. Expression of Human CD4 and chemokine receptors in cotton rat cells confers permissiveness for productive HIV infection

Author

Broder Christopher C, Stantchev Tzanko S, Khetawat Dimple, Wieczorek Lindsay, Pletneva Lioubov M, Blanco Jorge CG, Polonis Victoria R, and Prince Gregory A

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Current small animal models for studying HIV-1 infection are very limited, and this continues to be a major obstacle for studying HIV-1 infection and pathogenesis, as well as for the urgent development and evaluation of effective anti-HIV-1 therapies and vaccines. Previously, it was shown that HIV-1 can infect cotton rats as indicated by development of antibodies against all major proteins of the virus, the detection of viral cDNA in spleen and brain of challenged animals, the transmission of infectious virus, albeit with low efficiency, from animal to animal by blood, and an additional increase in the mortality in the infected groups. Results Using in vitro experiments, we now show that cotton rat cell lines engineered to express human receptor complexes for HIV-1 (hCD4 along with hCXCR4 or hCCR5) support virus entry, viral cDNA integration, and the production of infectious virus. Conclusion These results further suggest that the development of transgenic cotton rats expressing human HIV-1 receptors may prove to be useful small animal model for HIV infection.

Published
2009
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33. Neutralization Sensitivity of a Novel HIV-1 CRF01_AE Panel of Infectious Molecular Clones

Author

Chenine, Agnes-Laurence, primary, Merbah, Melanie, additional, Wieczorek, Lindsay, additional, Molnar, Sebastian, additional, Mann, Brendan, additional, Lee, Jenica, additional, O'Sullivan, Anne-Marie, additional, Bose, Meera, additional, Sanders-Buell, Eric, additional, Kijak, Gustavo H., additional, Herrera, Carolina, additional, McLinden, Robert, additional, O'Connell, Robert J., additional, Michael, Nelson L., additional, Robb, Merlin L., additional, Kim, Jerome H., additional, Polonis, Victoria R., additional, and Tovanabutra, Sodsai, additional

Published
2018
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34. HPA axis dysregulation and behavioral analysis of mouse mutants with altered GR or MR function

Author

Kolber, Benedict J., Wieczorek, Lindsay, and Muglia, Louis J.

Subjects
Mice, Knockout, Hypothalamo-Hypophyseal System, Memory Disorders, Behavior, Animal, Learning Disabilities, Pituitary-Adrenal System, Mice, Transgenic, Anxiety, Article, Mice, Mutant Strains, Circadian Rhythm, Mice, Prosencephalon, Receptors, Glucocorticoid, Receptors, Mineralocorticoid, Animals, Stress, Psychological
Abstract

Corticosteroid receptors are critical for the maintenance of homeostasis after both psychological and physiological stress. To understand the different roles and interactions of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) during stress, it is necessary to dissect the role of corticosteroid signaling at both the system and sub-system level. A variety of GR transgenic mouse lines have recently been used to characterize the role of GR in the CNS as a whole and particularly in the forebrain. We will describe both the behavioral and cellular/molecular implications of disrupting GR function in these animal models and describe the implications of this data for our understanding of normal endocrine function and stress adaptation. MRs in tight epithelia have a long established role in sodium homeostasis. Recently however, evidence has suggested that MRs in the limbic brain also play an important role in psychological stress. Just as with GR, targeted mutations in MR induce a variety of behavioral changes associated with stress adaptation. In this review, we will discuss the implications of this work on MR. Finally, we will discuss the possible interaction between MR and GR and how future work using double mutants (through conventional means or virus based gene alteration) will be needed to more fully understand how signaling through these two steroid receptors provides the adaptive mechanisms to deal with a variety of stressors.

Published
2008

35. Mitigation of variation observed in a peripheral blood mononuclear cell (PBMC) based HIV-1 neutralization assay by donor cell pooling

Author

Wieczorek, Lindsay, primary, Brown, Bruce K., additional, DelSarto Macedo, Camila, additional, Wesberry-Schmierer, Maggie, additional, Ngauy, Viseth, additional, Rosa Borges, Andrew, additional, Michael, Nelson L., additional, Marovich, Mary A., additional, Montefiori, David C., additional, and Polonis, Victoria R., additional

Published
2013
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36. Impact of HIV-1 Backbone on Neutralization Sensitivity: Neutralization Profiles of Heterologous Envelope Glycoproteins Expressed in Native Subtype C and CRF01_AE Backbone

Author

Chenine, Agnès-Laurence, primary, Wieczorek, Lindsay, additional, Sanders-Buell, Eric, additional, Wesberry, Maggie, additional, Towle, Teresa, additional, Pillis, Devin M., additional, Molnar, Sebastian, additional, McLinden, Robert, additional, Edmonds, Tara, additional, Hirsch, Ivan, additional, O’Connell, Robert, additional, McCutchan, Francine E., additional, Montefiori, David C., additional, Ochsenbauer, Christina, additional, Kappes, John C., additional, Kim, Jerome H., additional, Polonis, Victoria R., additional, and Tovanabutra, Sodsai, additional

Published
2013
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37. Detection of HIV-1 Neutralizing Antibodies in a Human CD4+/CXCR4+/CCR5+ T-Lymphoblastoid Cell Assay System

Author

McLinden, Robert J., primary, LaBranche, Celia C., additional, Chenine, Agnès-Laurence, additional, Polonis, Victoria R., additional, Eller, Michael A., additional, Wieczorek, Lindsay, additional, Ochsenbauer, Christina, additional, Kappes, John C., additional, Perfetto, Stephen, additional, Montefiori, David C., additional, Michael, Nelson L., additional, and Kim, Jerome H., additional

Published
2013
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38. Designing a Soluble Near Full-Length HIV-1 GP41 Trimer

Author

WALTER REED ARMY INST OF RESEARCH ROCKVILLE MD US MILITARY HIV RESEARCH PROGRAM/DIVISION OF RETROVIROLOGY, Gao, Guofen, Wieczorek, Lindsay, Peachman, Kristina K, Polonis, Victoria R, Alving, Carl R, Rao, Mangala, Rao, Venigalla B, WALTER REED ARMY INST OF RESEARCH ROCKVILLE MD US MILITARY HIV RESEARCH PROGRAM/DIVISION OF RETROVIROLOGY, Gao, Guofen, Wieczorek, Lindsay, Peachman, Kristina K, Polonis, Victoria R, Alving, Carl R, Rao, Mangala, and Rao, Venigalla B

Abstract

The HIV-1 envelope spike is a trimer of heterodimers composed of an external glycoprotein gp120 and a transmembrane glycoprotein gp41. gp120 initiates virus entry by binding to host receptors whereas gp41 mediates fusion between viral and host membranes. Although the basic pathway of HIV-1 entry has been extensively studied, the detailed mechanism is still poorly understood. Design of gp41 recombinants that mimic key intermediates is essential to elucidate the mechanism as well as to develop potent therapeutics and vaccines. Here, using molecular genetics and biochemical approaches, a series of hypotheses were tested to overcome the extreme hydrophobicity of HIV-1 gp41 and design a soluble near full-length gp41 trimer. The two long heptad repeat helices HR1 and HR2 of gp41 ectodomain were mutated to disrupt intra-molecular HR1-HR2 interactions but not inter-molecular HR1-HR1 interactions. This resulted in reduced aggregation and improved solubility. Attachment of a 27-aa foldon at the C-terminus and slow refolding channeled gp41 into trimers. The trimers appear to be stabilized in a prehairpin-like structure, as evident from binding of a HR2 peptide to exposed HR1 grooves, lack of binding to hexa-helical bundle-specific NC-1 mAb, and inhibition of virus neutralization by broadly neutralizing antibodies 2F5 and 4E10. Fusion to T4 small outer capsid protein, Soc, allowed display of gp41 trimers on the phage nanoparticle. These approaches for the first time led to the design of a soluble gp41 trimer containing both the fusion peptide and the cytoplasmic domain, providing insights into mechanism of entry and development of gp41-based HIV-1 vaccines., In JBC Papers in Press, published 26 Nov 2012.

Published
2012

39. The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization

Author

WALTER REED ARMY INST OF RESEARCH ROCKVILLE MD US MILITARY HIV RESEARCH PROGRAM/DIVISION OF RETROVIROLOGY, Brown, Bruce K, Wieczorek, Lindsay, Kijak, Gustavo, Lombardi, Kara, Currier, Jeffrey, Wesberry, Maggie, Kappes, John C, Ngauy, Viseth, Marovich, Mary, Michael, Nelson, WALTER REED ARMY INST OF RESEARCH ROCKVILLE MD US MILITARY HIV RESEARCH PROGRAM/DIVISION OF RETROVIROLOGY, Brown, Bruce K, Wieczorek, Lindsay, Kijak, Gustavo, Lombardi, Kara, Currier, Jeffrey, Wesberry, Maggie, Kappes, John C, Ngauy, Viseth, Marovich, Mary, and Michael, Nelson

Abstract

The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative donor PBMC for an impact on the anti-HIV activity of polyclonal and monoclonal antibodies. NK cell percentages were significantly higher in donor PBMC that supported lower levels of viral replication. While the percentage of NK cells was not directly associated with neutralization titers, NK celldepletion significantly diminished the antiviral antibody activity by up to three logs, and polymorphisms in NK killer immunoglobulin receptor (KIR) and FccRIIIa alleles appear to be associated with this affect. These findings demonstrate that NK cells and NK cell receptor polymorphisms may influence assessment of traditional HIV-1 neutralization in a platform where antibody is continuously present. This format appears to simultaneously assess conventional entry inhibition (neutralization) and non-neutralizing antibody-dependent HIV inhibition, which may provide the opportunity to delineate the dominant antibody function(s) in polyclonal vaccine responses., Published in PLoS ONE, v7, n4, p1-11, April 11, 2012. The original document contains color images.

Published
2012

40. Phase 1 Study of Safety and Immunogenicity of an Escherichia coli-Derived Recombinant Protective Antigen (rPA) Vaccine to Prevent Anthrax in Adults

Author

HENRY M JACKSON FOUNDATION ROCKVILLE MD, Brown, Bruce K., Cox, Josephine, Gillis, Anita, VanCott, Thomas C., Marovich, Mary, Milazzo, Mark, Antonille, Tanya S., Wieczorek, Lindsay, McKee, Jr., Kelly T., Metcalfe, Karen, HENRY M JACKSON FOUNDATION ROCKVILLE MD, Brown, Bruce K., Cox, Josephine, Gillis, Anita, VanCott, Thomas C., Marovich, Mary, Milazzo, Mark, Antonille, Tanya S., Wieczorek, Lindsay, McKee, Jr., Kelly T., and Metcalfe, Karen

Abstract

Background: The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA). Methodology/Principal Findings: A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 mg/ml AlhydrogelH adjuvant in increasing doses (5, 25, 50, 100 mg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 mg of rPA formulated with AlhydrogelH with a geometric mean concentration of anti-rPA IgG antibodies of 283 mg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 mg AlhydrogelH-formulated rPA. Conclusions/Significance: The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses., Published in the Public Library of Science (PLoS ONE), v5 i11 e13849, 2010. Prepared in cooperation with Walter Reed Army Institute of Research, Rockville, MD, and DynPort Vaccine Co. LLC, Frederick, MD.

Published
2010

42. The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization

Author

Brown, Bruce K., primary, Wieczorek, Lindsay, additional, Kijak, Gustavo, additional, Lombardi, Kara, additional, Currier, Jeffrey, additional, Wesberry, Maggie, additional, Kappes, John C., additional, Ngauy, Viseth, additional, Marovich, Mary, additional, Michael, Nelson, additional, Ochsenbauer, Christina, additional, Montefiori, David C., additional, and Polonis, Victoria R., additional

Published
2012
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43. Replication competent molecular clones of HIV-1 expressing Renilla luciferase facilitate the analysis of antibody inhibition in PBMC

Author

Edmonds, Tara G., primary, Ding, Haitao, additional, Yuan, Xing, additional, Wei, Qing, additional, Smith, Kendra S., additional, Conway, Joan A., additional, Wieczorek, Lindsay, additional, Brown, Bruce, additional, Polonis, Victoria, additional, West, John T., additional, Montefiori, David C., additional, Kappes, John C., additional, and Ochsenbauer, Christina, additional

Published
2010
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44. Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1

Author

Rosa Borges, Andrew, primary, Wieczorek, Lindsay, additional, Johnson, Benitra, additional, Benesi, Alan J., additional, Brown, Bruce K., additional, Kensinger, Richard D., additional, Krebs, Fred C., additional, Wigdahl, Brian, additional, Blumenthal, Robert, additional, Puri, Anu, additional, McCutchan, Francine E., additional, Birx, Deborah L., additional, Polonis, Victoria R., additional, and Schengrund, Cara-Lynne, additional

Published
2010
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46. Phase I Study of Safety and Immunogenicity of an Escherichia coli-Derived Recombinant Protective Antigen (rPA) Vaccine to Prevent Anthrax in Adults

Author

Brown, Bruce K., primary, Cox, Josephine, additional, Gillis, Anita, additional, VanCott, Thomas C., additional, Marovich, Mary, additional, Milazzo, Mark, additional, Antonille, Tanya Santelli, additional, Wieczorek, Lindsay, additional, McKee, Kelly T., additional, Metcalfe, Karen, additional, Mallory, Raburn M., additional, Birx, Deborah, additional, Polonis, Victoria R., additional, and Robb, Merlin L., additional

Published
2010
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