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Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies.

Publication ,  Journal Article
Kim, M; Qiao, Z-S; Montefiori, DC; Haynes, BF; Reinherz, EL; Liao, H-X
Published in: AIDS Res Hum Retroviruses
January 2005

Designing an immunogen for effective neutralizing antibody induction against diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) is a high priority for HIV-1 vaccine development. Soluble gp120 envelope (Env) glycoprotein subunit vaccines elicit high titers of antibodies that neutralize T cell line-adapted (TCLA) strains but the antibodies possess poor neutralizing activity against many primary isolates. Previously, we generated soluble trimeric recombinant gp140 from the HIV-1 primary isolate ADA. Here we compared monomeric ADAgp120 and trimeric ADAgp140 as immunogens for neutralizing antibody responses in guinea pigs. Both immunogens generated a neutralizing antibody response that was detectable against the vaccine strain and several heterologous strains. The magnitude of this response was significantly greater in ADAgp140-immunized animals when measured against the TCLA strain, MN, and the R5 primary isolate, Bal. Two additional isolates (SS1196 and Bx08) were neutralized equally by sera from both groups of animals whereas other isolates were neutralized weakly or not at all. Despite equal titers of V3 loop specific binding antibodies in sera from both groups of animals, neutralization of ADA by sera from gp140-immunized animals was insensitive to the presence of ADA-V3 peptide, whereas addition of this peptide to sera from gp120- immunized animals blocked all detectable neutralizing activity against ADA. These results support the idea that trimeric gp140 is an improved immunogen compared to monomeric gp120 but that additional improvements are required to afford broad protection against a spectrum of heterologous primary HIV-1 isolates. This ADAgp140 immunogen may be considered a starting point from which to engineer additional improvements for cross-reactive neutralizing antibody induction.

Duke Scholars

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Published In

AIDS Res Hum Retroviruses

DOI

ISSN

0889-2229

Publication Date

January 2005

Volume

21

Issue

1

Start / End Page

58 / 67

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Peptide Fragments
  • Neutralization Tests
  • Molecular Sequence Data
  • Immunization
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
 

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Kim, M., Qiao, Z.-S., Montefiori, D. C., Haynes, B. F., Reinherz, E. L., & Liao, H.-X. (2005). Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies. AIDS Res Hum Retroviruses, 21(1), 58–67. https://doi.org/10.1089/aid.2005.21.58
Kim, Mikyung, Zhi-Song Qiao, David C. Montefiori, Barton F. Haynes, Ellis L. Reinherz, and Hua-Xin Liao. “Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies.AIDS Res Hum Retroviruses 21, no. 1 (January 2005): 58–67. https://doi.org/10.1089/aid.2005.21.58.
Kim M, Qiao Z-S, Montefiori DC, Haynes BF, Reinherz EL, Liao H-X. Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies. AIDS Res Hum Retroviruses. 2005 Jan;21(1):58–67.
Kim, Mikyung, et al. “Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies.AIDS Res Hum Retroviruses, vol. 21, no. 1, Jan. 2005, pp. 58–67. Pubmed, doi:10.1089/aid.2005.21.58.
Kim M, Qiao Z-S, Montefiori DC, Haynes BF, Reinherz EL, Liao H-X. Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies. AIDS Res Hum Retroviruses. 2005 Jan;21(1):58–67.
Journal cover image

Published In

AIDS Res Hum Retroviruses

DOI

ISSN

0889-2229

Publication Date

January 2005

Volume

21

Issue

1

Start / End Page

58 / 67

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Peptide Fragments
  • Neutralization Tests
  • Molecular Sequence Data
  • Immunization
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120