HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV vaccine approach.
Adenoviral (Ad) vectors have been used for a variety of vaccine applications including cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen. However, in some cases these conventional Ad-based vaccines have had sub-optimal clinical results. These sub-optimal results are attributed in part to pre-existing Ad serotype 5 (Ad5) immunity. In order to circumvent the need for antigen expression via transgene incorporation, the "antigen capsid-incorporation" strategy has been developed and used for Ad-based vaccine development in the context of a few diseases. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. The major capsid protein hexon has been utilized for these capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion. Using this strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon. Our study herein focuses on generation of multivalent vaccine vectors presenting HIV antigens within the Ad capsid protein hexon, as well as expressing an HIV antigen as a transgene. These novel vectors utilize HVR2 as an incorporation site for a twenty-four amino acid region of the HIV membrane proximal ectodomain region (MPER), derived from HIV glycoprotein gp41 (gp41). Our study herein illustrates that our multivalent anti-HIV vectors elicit a cellular anti-HIV response. Furthermore, vaccinations with these vectors, which present HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response.
Matthews
Qiana L
QL
Division of Human Gene Therapy, Departments of Medicine, Pathology, Surgery, Obstetrics and Gynecology, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Fatima
Aiman
A
Tang
Yizhe
Y
Perry
Brian A
BA
Tsuruta
Yuko
Y
Komarova
Svetlana
S
Timares
Laura
L
Zhao
Chunxia
C
Makarova
Natalia
N
Borovjagin
Anton V
AV
Stewart
Phoebe L
PL
Wu
Hongju
H
Blackwell
Jerry L
JL
Curiel
David T
DT
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D015483:HIV Antibodies / Q000276:immunology; D015488:HIV Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015488:HIV Antigens; D015700:HIV Envelope Protein gp41; D010455:Peptides