Antigenicity and immunogenicity of transmitted/founder, consensus, and chronic envelope glycoproteins of human immunodeficiency virus type 1

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 pro...

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Published in:	Journal of virology Vol. 87; no. 8; p. 4185
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	United States 01.04.2013
Subjects:	Animals Antibodies, Neutralizing - blood Antibody Affinity Antigens, Viral - genetics Antigens, Viral - immunology Cross Reactions env Gene Products, Human Immunodeficiency Virus - genetics env Gene Products, Human Immunodeficiency Virus - immunology Glycoproteins - genetics Glycoproteins - immunology Guinea Pigs HIV Antibodies - blood HIV-1 - genetics HIV-1 - immunology HIV-1 - isolation & purification Humans
ISSN:	1098-5514, 1098-5514
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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.
AbstractList	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.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. 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.
Author	Foulger, Andrew Parks, Robert Watson, Sydeaka Lu, Xiaozhi Swanstrom, Ron Haynes, Barton F Lapedes, Alan Sutherland, Laura L Scearce, Richard M Xia, Shi-Mao Hahn, Beatrice H Korber, Bette Chen, Haiyan Muldoon, Mark Shaw, George M Blinn, Julie H Alam, S Munir Bowman, Cindy Liao, Hua-Xin Montefiori, David C Gao, Feng Ma, Ben-Jiang Tsao, Chun-Yen Vandergrift, Nathan
Author_xml	– sequence: 1 givenname: Hua-Xin surname: Liao fullname: Liao, Hua-Xin email: hliao@duke.edu organization: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA. hliao@duke.edu – sequence: 2 givenname: Chun-Yen surname: Tsao fullname: Tsao, Chun-Yen – sequence: 3 givenname: S Munir surname: Alam fullname: Alam, S Munir – sequence: 4 givenname: Mark surname: Muldoon fullname: Muldoon, Mark – sequence: 5 givenname: Nathan surname: Vandergrift fullname: Vandergrift, Nathan – sequence: 6 givenname: Ben-Jiang surname: Ma fullname: Ma, Ben-Jiang – sequence: 7 givenname: Xiaozhi surname: Lu fullname: Lu, Xiaozhi – sequence: 8 givenname: Laura L surname: Sutherland fullname: Sutherland, Laura L – sequence: 9 givenname: Richard M surname: Scearce fullname: Scearce, Richard M – sequence: 10 givenname: Cindy surname: Bowman fullname: Bowman, Cindy – sequence: 11 givenname: Robert surname: Parks fullname: Parks, Robert – sequence: 12 givenname: Haiyan surname: Chen fullname: Chen, Haiyan – sequence: 13 givenname: Julie H surname: Blinn fullname: Blinn, Julie H – sequence: 14 givenname: Alan surname: Lapedes fullname: Lapedes, Alan – sequence: 15 givenname: Sydeaka surname: Watson fullname: Watson, Sydeaka – sequence: 16 givenname: Shi-Mao surname: Xia fullname: Xia, Shi-Mao – sequence: 17 givenname: Andrew surname: Foulger fullname: Foulger, Andrew – sequence: 18 givenname: Beatrice H surname: Hahn fullname: Hahn, Beatrice H – sequence: 19 givenname: George M surname: Shaw fullname: Shaw, George M – sequence: 20 givenname: Ron surname: Swanstrom fullname: Swanstrom, Ron – sequence: 21 givenname: David C surname: Montefiori fullname: Montefiori, David C – sequence: 22 givenname: Feng surname: Gao fullname: Gao, Feng – sequence: 23 givenname: Barton F surname: Haynes fullname: Haynes, Barton F – sequence: 24 givenname: Bette surname: Korber fullname: Korber, Bette
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Snippet	Human immunodeficiency virus type 1 (HIV-1) vaccine development requires selection of appropriate envelope (Env) immunogens. Twenty HIV-1 Env glycoproteins...
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SubjectTerms	Animals Antibodies, Neutralizing - blood Antibody Affinity Antigens, Viral - genetics Antigens, Viral - immunology Cross Reactions env Gene Products, Human Immunodeficiency Virus - genetics env Gene Products, Human Immunodeficiency Virus - immunology Glycoproteins - genetics Glycoproteins - immunology Guinea Pigs HIV Antibodies - blood HIV-1 - genetics HIV-1 - immunology HIV-1 - isolation & purification Humans
Title	Antigenicity and immunogenicity of transmitted/founder, consensus, and chronic envelope glycoproteins of human immunodeficiency virus type 1
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