HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV vaccine approach

Qiana L. Matthews, Aiman Fatima, Yizhe Tang, Brian A. Perry, Yuko Tsuruta, Svetlana Komarova, Laura Timares, Chunxia Zhao, Natalia Makarova, Anton V. Borovjagin, Phoebe L. Stewart, Hongju Wu, Jerry L. Blackwell, David T. Curiel

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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 Adbased 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.

Original languageEnglish (US)
Article numbere11815
JournalPLoS One
Volume5
Issue number7
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

HIV Antigens
AIDS Vaccines
Adenoviridae
Vaccines
vaccines
Capsid
antigens
Capsid Proteins
Transgenes
HIV
Antigens
capsid
coat proteins
transgenes
Epitopes
HIV Envelope Protein gp41
epitopes
Viral Structures
Peptides
Humoral Immunity

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Matthews, Q. L., Fatima, A., Tang, Y., Perry, B. A., Tsuruta, Y., Komarova, S., ... Curiel, D. T. (2010). HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV vaccine approach. PLoS One, 5(7), [e11815]. https://doi.org/10.1371/journal.pone.0011815

HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV vaccine approach. / 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.

In: PLoS One, Vol. 5, No. 7, e11815, 2010.

Research output: Contribution to journalArticle

Matthews, QL, Fatima, A, Tang, Y, Perry, BA, Tsuruta, Y, Komarova, S, Timares, L, Zhao, C, Makarova, N, Borovjagin, AV, Stewart, PL, Wu, H, Blackwell, JL & Curiel, DT 2010, 'HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV vaccine approach', PLoS One, vol. 5, no. 7, e11815. https://doi.org/10.1371/journal.pone.0011815
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. / HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV vaccine approach. In: PLoS One. 2010 ; Vol. 5, No. 7.
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