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2. Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys

Author

Santra, Sampa, Liao, Hua-Xin, Zhang, Ruijin, Muldoon, Mark, Watson, Sydeaka, Fischer, Will, Theiler, James, Szinger, James, Balachandran, Harikrishnan, Buzby, Adam, Quinn, David, Parks, Robert J, Tsao, Chun-Yen, Carville, Angela, Mansfield, Keith G, Pavlakis, George N, Felber, Barbara K, Haynes, Barton F, Korber, Bette T, and Letvin, Norman L

Published
2010
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4. 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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6. Mosaic Vaccines Elicit CD8+ T lymphocyte Responses in Monkeys that Confer Enhanced Immune Coverage of Diverse HIV Strains

Author

Santra, Sampa, Liao, Hua-Xin, Zhang, Ruijin, Muldoon, Mark, Watson, Sydeaka, Fischer, Will, Theiler, James, Szinger, James, Balachandran, Harikrishnan, Buzby, Adam, Quinn, David, Parks, Robert J., Tsao, Chun-Yen, Carville, Angela, Mansfield, Keith G., Pavlakis, George N., Felber, Barbara K., Haynes, Barton F., Korber, Bette T., and Letvin, Norman L.

Subjects
AIDS Vaccines, Immunity, Cellular, Vaccines, Synthetic, HIV Protease, HIV Antigens, T-Lymphocytes, HIV-1, env Gene Products, Human Immunodeficiency Virus, Animals, Epitopes, T-Lymphocyte, Macaca mulatta, gag Gene Products, Human Immunodeficiency Virus, Article
Abstract

An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses1, 2. It must generate CD8+ T lymphocytes that control HIV replication and CD4+ T lymphocytes that provide help for the generation and maintenance of both cellular and humoral immune responses against the virus3–5. Creating immunogens that can elicit cellular immune responses against the genetically varied circulating isolates of HIV presents an important challenge for creating an AIDS vaccine6, 7. Polyvalent mosaic immunogens derived by in silico recombination of natural strains of HIV are designed to induce cellular immune responses that recognize genetically diverse circulating virus isolates8. In the present study we immunized rhesus monkeys by plasmid DNA prime/ recombinant vaccinia virus boost using vaccine constructs expressing either consensus or polyvalent mosaic proteins. The mosaic immunogens elicited CD8+ T lymphocyte responses to more epitopes of each viral protein than the consensus immunogens, and to more variant sequences of CD8+ T lymphocyte epitopes. This increased breadth and depth of epitope recognition may contribute both to protection against infection by genetically diverse viruses and to the control of variant viruses that emerge as they mutate away from recognition by cytotoxic T lymphocytes.

Published
2010

8. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1

Author

Liao, Hua-Xin, primary, Tsao, Chun-Yen, additional, Alam, S. Munir, additional, Muldoon, Mark, additional, Vandergrift, Nathan, additional, Ma, Ben-Jiang, additional, Lu, Xiaozhi, additional, Sutherland, Laura L., additional, Scearce, Richard M., additional, Bowman, Cindy, additional, Parks, Robert, additional, Chen, Haiyan, additional, Blinn, Julie H., additional, Lapedes, Alan, additional, Watson, Sydeaka, additional, Xia, Shi-Mao, additional, Foulger, Andrew, additional, Hahn, Beatrice H., additional, Shaw, George M., additional, Swanstrom, Ron, additional, Montefiori, David C., additional, Gao, Feng, additional, Haynes, Barton F., additional, and Korber, Bette, additional

Published
2013
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9. Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion

Author

Alam, S. Munir, primary, Liao, Hua-Xin, additional, Tomaras, Georgia D., additional, Bonsignori, Mattia, additional, Tsao, Chun-Yen, additional, Hwang, Kwan-Ki, additional, Chen, Haiyan, additional, Lloyd, Krissey E., additional, Bowman, Cindy, additional, Sutherland, Laura, additional, Jeffries, Thomas L., additional, Kozink, Daniel M., additional, Stewart, Shelley, additional, Anasti, Kara, additional, Jaeger, Frederick H., additional, Parks, Robert, additional, Yates, Nicole L., additional, Overman, R. Glenn, additional, Sinangil, Faruk, additional, Berman, Phillip W., additional, Pitisuttithum, Punnee, additional, Kaewkungwal, Jaranit, additional, Nitayaphan, Sorachai, additional, Karasavva, Nicos, additional, Rerks-Ngarm, Supachai, additional, Kim, Jerome H., additional, Michael, Nelson L., additional, Zolla-Pazner, Susan, additional, Santra, Sampa, additional, Letvin, Norman L., additional, Harrison, Stephen C., additional, and Haynes, Barton F., additional

Published
2013
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10. Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies from an HIV-1 Vaccine Efficacy Trial Target Multiple Epitopes and Preferentially Use the VH1 Gene Family

Author

Bonsignori, Mattia, primary, Pollara, Justin, additional, Moody, M. Anthony, additional, Alpert, Michael D., additional, Chen, Xi, additional, Hwang, Kwan-Ki, additional, Gilbert, Peter B., additional, Huang, Ying, additional, Gurley, Thaddeus C., additional, Kozink, Daniel M., additional, Marshall, Dawn J., additional, Whitesides, John F., additional, Tsao, Chun-Yen, additional, Kaewkungwal, Jaranit, additional, Nitayaphan, Sorachai, additional, Pitisuttithum, Punnee, additional, Rerks-Ngarm, Supachai, additional, Kim, Jerome H., additional, Michael, Nelson L., additional, Tomaras, Georgia D., additional, Montefiori, David C., additional, Lewis, George K., additional, DeVico, Anthony, additional, Evans, David T., additional, Ferrari, Guido, additional, Liao, Hua-Xin, additional, and Haynes, Barton F., additional

Published
2012
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11. Early Low-Titer Neutralizing Antibodies Impede HIV-1 Replication and Select for Virus Escape

Author

Bar, Katharine J., primary, Tsao, Chun-yen, additional, Iyer, Shilpa S., additional, Decker, Julie M., additional, Yang, Yongping, additional, Bonsignori, Mattia, additional, Chen, Xi, additional, Hwang, Kwan-Ki, additional, Montefiori, David C., additional, Liao, Hua-Xin, additional, Hraber, Peter, additional, Fischer, William, additional, Li, Hui, additional, Wang, Shuyi, additional, Sterrett, Sarah, additional, Keele, Brandon F., additional, Ganusov, Vitaly V., additional, Perelson, Alan S., additional, Korber, Bette T., additional, Georgiev, Ivelin, additional, McLellan, Jason S., additional, Pavlicek, Jeffrey W., additional, Gao, Feng, additional, Haynes, Barton F., additional, Hahn, Beatrice H., additional, Kwong, Peter D., additional, and Shaw, George M., additional

Published
2012
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12. Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design

Author

Bonsignori, Mattia, primary, Montefiori, David C., additional, Wu, Xueling, additional, Chen, Xi, additional, Hwang, Kwan-Ki, additional, Tsao, Chun-Yen, additional, Kozink, Daniel M., additional, Parks, Robert J., additional, Tomaras, Georgia D., additional, Crump, John A., additional, Kapiga, Saidi H., additional, Sam, Noel E., additional, Kwong, Peter D., additional, Kepler, Thomas B., additional, Liao, Hua-Xin, additional, Mascola, John R., additional, and Haynes, Barton F., additional

Published
2012
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13. Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors

Author

Bonsignori, Mattia, primary, Hwang, Kwan-Ki, additional, Chen, Xi, additional, Tsao, Chun-Yen, additional, Morris, Lynn, additional, Gray, Elin, additional, Marshall, Dawn J., additional, Crump, John A., additional, Kapiga, Saidi H., additional, Sam, Noel E., additional, Sinangil, Faruk, additional, Pancera, Marie, additional, Yongping, Yang, additional, Zhang, Baoshan, additional, Zhu, Jiang, additional, Kwong, Peter D., additional, O'Dell, Sijy, additional, Mascola, John R., additional, Wu, Lan, additional, Nabel, Gary J., additional, Phogat, Sanjay, additional, Seaman, Michael S., additional, Whitesides, John F., additional, Moody, M. Anthony, additional, Kelsoe, Garnett, additional, Yang, Xinzhen, additional, Sodroski, Joseph, additional, Shaw, George M., additional, Montefiori, David C., additional, Kepler, Thomas B., additional, Tomaras, Georgia D., additional, Alam, S. Munir, additional, Liao, Hua-Xin, additional, and Haynes, Barton F., additional

Published
2011
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16. DNA Vaccine Expressing the Mimotope of GD2 Ganglioside Induces Protective GD2 Cross-reactive Antibody Responses

Author

Bolesta, Elizabeth, primary, Kowalczyk, Aleksandra, additional, Wierzbicki, Andrzej, additional, Rotkiewicz, Piotr, additional, Bambach, Barbara, additional, Tsao, Chun-Yen, additional, Horwacik, Irena, additional, Kolinski, Andrzej, additional, Rokita, Hanna, additional, Brecher, Martin, additional, Wang, Xinhui, additional, Ferrone, Soldano, additional, and Kozbor, Danuta, additional

Published
2005
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17. Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys

Author

Santra, Sampa, Liao, Hua-Xin, Zhang, Ruijin, Muldoon, Mark, Watson, Sydeaka, Fischer, Will, Theiler, James, Szinger, James, Balachandran, Harikrishnan, Buzby, Adam, Quinn, David, Parks, Robert J., Tsao, Chun-Yen, Carville, Angela, Mansfield, Keith G., Pavlakis, George N., Felber, Barbara K., Haynes, Barton F., Korber, Bette T., Letvin, Norman L., Santra, Sampa, Liao, Hua-Xin, Zhang, Ruijin, Muldoon, Mark, Watson, Sydeaka, Fischer, Will, Theiler, James, Szinger, James, Balachandran, Harikrishnan, Buzby, Adam, Quinn, David, Parks, Robert J., Tsao, Chun-Yen, Carville, Angela, Mansfield, Keith G., Pavlakis, George N., Felber, Barbara K., Haynes, Barton F., Korber, Bette T., and Letvin, Norman L.

Abstract

An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses. It must generate CD8+ T lymphocytes that control HIV replication and CD4+ T lymphocytes that provide help for the generation and maintenance of both cellular and humoral immune responses against the virus. Creating immunogens that can elicit cellular immune responses against the genetically varied circulating isolates of HIV presents a key challenge for creating an HIV vaccine. Polyvalent mosaic immunogens derived by in silico recombination of natural strains of HIV are designed to induce cellular immune responses that recognize genetically diverse circulating virus isolates8. Here we immunized rhesus monkeys by plasmid DNA prime and recombinant vaccinia virus boost with vaccine constructs expressing either consensus or polyvalent mosaic proteins. As compared to consensus immunogens, the mosaic immunogens elicited CD8+ T lymphocyte responses to more epitopes of each viral protein than did the consensus immunogens and to more variant sequences of CD8+ T lymphocyte epitopes. This increased breadth and depth of epitope recognition may contribute both to protection against infection by genetically diverse viruses and to the control of variant viruses that emerge as they mutate away from recognition by cytotoxic T lymphocytes.

18. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus, and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1

Author

Liao, Hua-Xin, Tsao, Chun-Yen, Alam, S. Munir, Muldoon, Mark, Vandergrift, Nathan, Ma, Ben-Jiang, Lu, Xiaozhi, Sutherland, Laura L, Scearce, Richard M., Bowman, Cindy, Parks, Robert, Chen, Haiyan, Blinn, Julie H, Lapedes, Alan, Watson, Sydeaka, Xia, Shi-Mao, Foulger, Andrew, Hahn, Beatrice H, Shaw, George M, Swanstrom, Ron, Montefiori, David C, Gao, Feng, Haynes, Barton F, Korber, Bette, Liao, Hua-Xin, Tsao, Chun-Yen, Alam, S. Munir, Muldoon, Mark, Vandergrift, Nathan, Ma, Ben-Jiang, Lu, Xiaozhi, Sutherland, Laura L, Scearce, Richard M., Bowman, Cindy, Parks, Robert, Chen, Haiyan, Blinn, Julie H, Lapedes, Alan, Watson, Sydeaka, Xia, Shi-Mao, Foulger, Andrew, Hahn, Beatrice H, Shaw, George M, Swanstrom, Ron, Montefiori, David C, Gao, Feng, Haynes, Barton F, and Korber, Bette

Abstract

Human immunodeficiency virus type 1 (HIV-1) vaccine development requires selection of appropriate envelope (Env) immunogens. Twenty HIV-1 Env glycoproteins were examined for their ability to bind human anti-HIV-1 monoclonal antibodies (MAbs) and then used as immunogens in guinea pigs to identify promising immunogens. These included five Envs derived from chronically infected individuals, each representing one of five common clades and eight consensus Envs based on these five clades, as well as the consensus of the entire HIV-1 M group, and seven transmitted/founder (T/F) Envs from clades B and C. Sera from immunized guinea pigs were tested for neutralizing activity using 36 HIV-1 Env-pseudotyped viruses. All Envs bound to CD4 binding site, membrane-proximal, and V1/V2 MAbs with similar apparent affinities, although the T/F Envs bound with higher affinity to the MAb 17b, a CCR5 coreceptor binding site antibody. However, the various Envs differed in their ability to induce neutralizing antibodies. Consensus Envs elicited the most potent responses, but neutralized only a subset of viruses, including mostly easy-to-neutralize tier 1 and some more-difficult-to-neutralize tier 2 viruses. T/F Envs elicited fewer potent neutralizing antibodies but exhibited greater breadth than chronic or consensus Envs. Finally, chronic Envs elicited the lowest level and most limited breadth of neutralizing antibodies overall. Thus, each group of Env immunogens elicited a different antibody response profile. The complementary benefits of consensus and T/F Env immunogens raise the possibility that vaccines utilizing a combination of consensus and T/F Envs may be able to induce neutralizing responses with greater breadth and potency than single Env immunogens.

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