Adenoviral vectors elicit humoral immunity against variable loop 2 of clade C HIV-1 gp120 via "Antigen Capsid-Incorporation" strategy

被引:7
作者
Gu, Linlin [1 ]
Krendelchtchikova, Valentina [1 ]
Krendelchtchikov, Alexandre [1 ]
Farrow, Anitra L. [1 ]
Derdeyn, Cynthia A. [2 ,3 ]
Matthews, Qiana L. [1 ,4 ]
机构
[1] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Birmingham, AL 35294 USA
[2] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30329 USA
[3] Emory Univ, Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA
[4] Univ Alabama Birmingham, Ctr AIDS Res, Birmingham, AL 35294 USA
基金
美国国家卫生研究院;
关键词
HIV-1; vaccine; Adenoviral (Ad) vector; Antigen Capsid-Incorporation" strategy; Variable loop2 (V2); Humoral immunity; IgG isotypes; EFFICACY TRIAL; DOUBLE-BLIND; VACCINE; ANTIBODIES; IMMUNOGENICITY; PROTECTION; ACQUISITION; CHALLENGE; INFECTION; SAFETY;
D O I
10.1016/j.virol.2015.10.010
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Adenoviral (Ad) vectors in combination with the "Antigen Capsid-Incorporation" strategy have been applied in developing HIV-1 vaccines, due to the vectors' abilities in incorporating and inducing immunity of capsid-incorporated antigens. Variable loop 2 (V2)-specific antibodies were suggested in the RV144 trial to correlate with reduced HIV-1 acquisition, which highlights the importance of developing novel HIV-1 vaccines by targeting the V2 loop. Therefore, the V2 loop of HIV-1 has been incorporated into the Ad capsid protein. We generated adenovirus serotype 5 (Ad5) vectors displaying variable loop 2 (V2) of HIV-1 gp120, with the "Antigen Capsid-Incorporation" strategy. To assess the incorporation capabilities on hexon hypervariable region! (HVR1) and protein IX (pIX), 20aa or full length (43aa) of V2 and V1V2 (67aa) were incorporated, respectively. Immunizations with the recombinant vectors significantly generated antibodies against both linear and discontinuous V2 epitopes. The immunizations generated durable humoral immunity against V2. This study will lead to more stringent development of various serotypes of adenovirus-vectored V2 vaccine candidates, based on breakthroughs regarding the immunogenicity of V2. (C) 2015 Published by Elsevier Inc.
引用
收藏
页码:75 / 84
页数:10
相关论文
共 37 条
[11]   Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine [J].
Hammer, Scott M. ;
Sobieszczyk, Magdalena E. ;
Janes, Holly ;
Karuna, Shelly T. ;
Mulligan, Mark J. ;
Grove, Doug ;
Koblin, Beryl A. ;
Buchbinder, Susan P. ;
Keefer, Michael C. ;
Tomaras, Georgia D. ;
Frahm, Nicole ;
Hural, John ;
Anude, Chuka ;
Graham, Barney S. ;
Enama, Mary E. ;
Adams, Elizabeth ;
DeJesus, Edwin ;
Novak, Richard M. ;
Frank, Ian ;
Bentley, Carter ;
Ramirez, Shelly ;
Fu, Rong ;
Koup, Richard A. ;
Mascola, John R. ;
Nabel, Gary J. ;
Montefiori, David C. ;
Kublin, James ;
McElrath, M. Juliana ;
Corey, Lawrence ;
Gilbert, Peter B. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (22) :2083-2092
[12]   Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial [J].
Haynes, Barton F. ;
Gilbert, Peter B. ;
McElrath, M. Juliana ;
Zolla-Pazner, Susan ;
Tomaras, Georgia D. ;
Alam, S. Munir ;
Evans, David T. ;
Montefiori, David C. ;
Karnasuta, Chitraporn ;
Sutthent, Ruengpueng ;
Liao, Hua-Xin ;
DeVico, Anthony L. ;
Lewis, George K. ;
Williams, Constance ;
Pinter, Abraham ;
Fong, Youyi ;
Janes, Holly ;
DeCamp, Allan ;
Huang, Yunda ;
Rao, Mangala ;
Billings, Erik ;
Karasavvas, Nicos ;
Robb, Merlin L. ;
Ngauy, Viseth ;
de Souza, Mark S. ;
Paris, Robert ;
Ferrari, Guido ;
Bailer, Robert T. ;
Soderberg, Kelly A. ;
Andrews, Charla ;
Berman, Phillip W. ;
Frahm, Nicole ;
De Rosa, Stephen C. ;
Alpert, Michael D. ;
Yates, Nicole L. ;
Shen, Xiaoying ;
Koup, Richard A. ;
Pitisuttithum, Punnee ;
Kaewkungwal, Jaranit ;
Nitayaphan, Sorachai ;
Rerks-Ngarm, Supachai ;
Michael, Nelson L. ;
Kim, Jerome H. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (14) :1275-1286
[13]   Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer [J].
Julien, Jean-Philippe ;
Cupo, Albert ;
Sok, Devin ;
Stanfield, Robyn L. ;
Lyumkis, Dmitry ;
Deller, Marc C. ;
Klasse, Per-Johan ;
Burton, Dennis R. ;
Sanders, Rogier W. ;
Moore, John P. ;
Ward, Andrew B. ;
Wilson, Ian A. .
SCIENCE, 2013, 342 (6165) :1477-1483
[14]   The Thai Phase III HIV Type 1 Vaccine Trial (RV144) Regimen Induces Antibodies That Target Conserved Regions Within the V2 Loop of gp120 [J].
Karasavvas, Nicos ;
Billings, Erik ;
Rao, Mangala ;
Williams, Constance ;
Zolla-Pazner, Susan ;
Bailer, Robert T. ;
Koup, Richard A. ;
Madnote, Sirinan ;
Arworn, Duangnapa ;
Shen, Xiaoying ;
Tomaras, Georgia D. ;
Currier, Jeffrey R. ;
Jiang, Mike ;
Magaret, Craig ;
Andrews, Charla ;
Gottardo, Raphael ;
Gilbert, Peter ;
Cardozo, Timothy J. ;
Rerks-Ngarm, Supachai ;
Nitayaphan, Sorachai ;
Pitisuttithum, Punnee ;
Kaewkungwal, Jaranit ;
Paris, Robert ;
Greene, Kelli ;
Gao, Hongmei ;
Gurunathan, Sanjay ;
Tartaglia, Jim ;
Sinangil, Faruk ;
Korber, Bette T. ;
Montefiori, David C. ;
Mascola, John R. ;
Robb, Merlin L. ;
Haynes, Barton F. ;
Ngauy, Viseth ;
Michael, Nelson L. ;
Kim, Jerome H. ;
de Souza, Mark S. .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2012, 28 (11) :1444-1457
[15]   Intraprotomer masking of third variable loop (V3) epitopes by the first and second variable loops (V1V2) within the native HIV-1 envelope glycoprotein trimer [J].
Liu, Li ;
Cimbro, Raffaello ;
Lusso, Paolo ;
Berger, Edward A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (50) :20148-20153
[16]   Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by immunization [J].
Lubeck, MD ;
Natuk, R ;
Myagkikh, M ;
Kalyan, N ;
Aldrich, K ;
Sinangil, F ;
Alipanah, S ;
Murthy, SCS ;
Chanda, PK ;
Nigida, SM ;
Markham, PD ;
ZollaPazner, S ;
Steimer, K ;
Wade, M ;
Reitz, MS ;
Arthur, LO ;
Mizutani, S ;
Davis, A ;
Hung, PP ;
Gallo, RC ;
Eichberg, J ;
RobertGuroff, M .
NATURE MEDICINE, 1997, 3 (06) :651-658
[17]   The B Cell Response Is Redundant and Highly Focused on V1V2 during Early Subtype C Infection in a Zambian Seroconverter [J].
Lynch, Rebecca M. ;
Rong, Rong ;
Boliar, Saikat ;
Sethi, Anurag ;
Li, Bing ;
Mulenga, Joseph ;
Allen, Susan ;
Robinson, James E. ;
Gnanakaran, S. ;
Derdeyn, Cynthia A. .
JOURNAL OF VIROLOGY, 2011, 85 (02) :905-915
[18]   HIV Antigen Incorporation within Adenovirus Hexon Hypervariable 2 for a Novel HIV Vaccine Approach [J].
Matthews, Qiana L. ;
Fatima, Aiman ;
Tang, Yizhe ;
Perry, Brian A. ;
Tsuruta, Yuko ;
Komarova, Svetlana ;
Timares, Laura ;
Zhao, Chunxia ;
Makarova, Natalia ;
Borovjagin, Anton V. ;
Stewart, Phoebe L. ;
Wu, Hongju ;
Blackwell, Jerry L. ;
Curiel, David T. .
PLOS ONE, 2010, 5 (07)
[19]   Epitope Mapping of Conformational V2-specific Anti-HIV Human Monoclonal Antibodies Reveals an Immunodominant Site in V2 [J].
Mayr, Luzia M. ;
Cohen, Sandra ;
Spurrier, Brett ;
Kong, Xiang-Peng ;
Zolla-Pazner, Susan .
PLOS ONE, 2013, 8 (07)
[20]   Monoclonal Antibodies to the V2 Domain of MN-rgp120: Fine Mapping of Epitopes and Inhibition of α4β7 Binding [J].
Nakamura, Gerald R. ;
Fonseca, Dora P. A. J. ;
O'Rourke, Sara M. ;
Vollrath, Aaron L. ;
Berman, Phillip W. .
PLOS ONE, 2012, 7 (06)