Broad HIV-1 neutralizing antibody response induced by heterologous gp140/gp145 DNA prime-vaccinia boost immunization.

Abstract

OBJECTIVE:

To develop an effective HIV vaccine strategy that can induce cross-reactive neutralizing antibody.

METHODS:

Codon-optimized gp140 and gp145 env genes derived from HIV-1(cn54), a CRF07 B'/C recombinant strain, were constructed as DNA and recombinant Tiantan vaccinia (rTV) vaccines. The effect of heterologous immunization with gp140 and gp145 was tested in mice and guinea pigs. T cell responses were detected using the IFN-γ ELISPOT assay. A panel of primary isolates of clade B' and B'/C HIV-1 and TZM-bl cells was used to determine the neutralizing activity of immunized sera.

RESULTS:

The neutralizing antibodies (NAbs) induced by the heterologous immunogen immunization neutralized all HIV-1 B' and B'/C primary isolates in the guinea pig model. Gp145 and gp140 heterologous prime-boost induced the best neutralizing antibody response with a broad neutralizing spectrum and the highest titer of 1:270 at 6 weeks after the last inoculation. However, the T cell response to HIV-1 peptides was significantly weaker than the gp145+gp145 homologous prime-boost.

CONCLUSIONS:

This heterologous prime-boost immunization strategy could be used to design immunogen-generating broad neutralizing antibodies against genetic variance pathogens.

• Authors: Lianxing Liu, Yanling Hao, Zhenwu Luo, Yang Huang, Xintao Hu, Ying Liu, Yiming Shao
• Journal: Vaccine (Vaccine) Vol. 30 Issue 28 Pg. 4135-43 (Jun 13 2012) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 22561314 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• AIDS Vaccines
• Antibodies, Neutralizing
• Antibodies, Viral
• Vaccines, DNA
• Vaccines, Subunit
• env Gene Products, Human Immunodeficiency Virus
• gp140 envelope protein, Human immunodeficiency virus 1
• Interferon-gamma

Topics

• AIDS Vaccines (administration & dosage, genetics, immunology)
• Animals
• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood)
• Enzyme-Linked Immunospot Assay
• Female
• Genetic Vectors
• Guinea Pigs
• HIV-1 (genetics, immunology)
• Interferon-gamma (metabolism)
• Mice
• Mice, Inbred BALB C
• Neutralization Tests
• T-Lymphocytes (immunology)
• Vaccination (methods)
• Vaccines, DNA (administration & dosage, genetics, immunology)
• Vaccines, Subunit (administration & dosage, genetics, immunology)
• Vaccinia virus (genetics)
• env Gene Products, Human Immunodeficiency Virus (genetics, immunology)