Adenoviral vectors elicit humoral immunity against variable loop 2 of clade C HIV-1 gp120 via "Antigen Capsid-Incorporation" strategy.
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 region1 (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.
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA.
Linlin
L
Gu
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA.
Valentina
V
Krendelchtchikova
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA.
Alexandre
A
Krendelchtchikov
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA.
Anitra L
AL
Farrow
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329, USA; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Cynthia A
CA
Derdeyn
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, 845 19th Street South, Birmingham, AL 35294, USA; Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: qlm@uab.edu.
Qiana L
QL
Matthews
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D036022:Capsid Proteins; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; C514793:gp120 protein, Human immunodeficiency virus 1
Adenoviral (Ad) vector; HIV-1 vaccine; Humoral immunity; IgG isotypes; Variable loop2 (V2); “Antigen Capsid-Incorporation” strategy