Humoral immunogenicity of an HIV-1 envelope residue 649-684 membrane-proximal region peptide fused to the plague antigen F1-V

Nobuyuki Matoba, Namrata Rahul Shah, Tsafrir Leket-Mor

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The membrane-proximal region spanning residues 649-684 of the HIV-1 envelope protein gp41 (MPR 649-684) is an attractive vaccine target for humoral immunity that blocks viral transcytosis across the mucosal epithelia. However, induction of high-titer MPR 649-684-specific antibodies remains a challenging task. To explore potential solutions for this challenge, we tested a new translational fusion protein comprising the plague F1-V antigen and MPR 649-684 (F1-V-MPR 649-684). We employed systemic immunization for initial feasibility analyses. Despite strong immunogenicity demonstrated for the immunogen, repeated systemic immunizations of mice with F1-V-MPR 649-684 hardly induced MPR 649-684-specific IgG. In contrast, a single immunization with F1-V-MPR 649-684 mounted a significant anti-MPR 649-684 IgG response in animals that were primed with another MPR 649-684 fusion protein based on the cholera toxin B subunit. Additional boost immunizations with F1-V-MPR 649-684 recalled and maintained the antibody response and expanded the number of specific antibody-secreting B cells. Thus, while F1-V-MPR 649-684 alone was not sufficiently immunogenic to induce detectable levels of MPR 649-684-specific antibodies, these results suggest that prime-boost immunization using heterologous antigen-display platforms may overcome the poor humoral immunogenicity of MPR 649-684 for the induction of durable humoral immunity. Further studies are warranted to evaluate the feasibility of this strategy in mucosal immunization. Lastly, our findings add to a growing body of evidence in support of this strategy for immunogen design for poorly immunogenic epitopes besides the MPR of HIV-1's transmembrane envelope protein.

Original languageEnglish (US)
Pages (from-to)5584-5590
Number of pages7
JournalVaccine
Volume29
Issue number34
DOIs
StatePublished - Aug 5 2011

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Plague
plague
Human immunodeficiency virus 1
HIV-1
Immunization
immunization
immune response
peptides
antigens
Antigens
Peptides
Membranes
antibodies
Humoral Immunity
humoral immunity
proteins
Immunoglobulin G
physiological transport
Heterophile Antigens
Transcytosis

Keywords

  • Fusion protein
  • Gp41 membrane proximal external region
  • HIV/AIDS
  • Plague F1-V antigen
  • Prime boost immunization
  • Subunit vaccine

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Humoral immunogenicity of an HIV-1 envelope residue 649-684 membrane-proximal region peptide fused to the plague antigen F1-V. / Matoba, Nobuyuki; Shah, Namrata Rahul; Leket-Mor, Tsafrir.

In: Vaccine, Vol. 29, No. 34, 05.08.2011, p. 5584-5590.

Research output: Contribution to journalArticle

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abstract = "The membrane-proximal region spanning residues 649-684 of the HIV-1 envelope protein gp41 (MPR 649-684) is an attractive vaccine target for humoral immunity that blocks viral transcytosis across the mucosal epithelia. However, induction of high-titer MPR 649-684-specific antibodies remains a challenging task. To explore potential solutions for this challenge, we tested a new translational fusion protein comprising the plague F1-V antigen and MPR 649-684 (F1-V-MPR 649-684). We employed systemic immunization for initial feasibility analyses. Despite strong immunogenicity demonstrated for the immunogen, repeated systemic immunizations of mice with F1-V-MPR 649-684 hardly induced MPR 649-684-specific IgG. In contrast, a single immunization with F1-V-MPR 649-684 mounted a significant anti-MPR 649-684 IgG response in animals that were primed with another MPR 649-684 fusion protein based on the cholera toxin B subunit. Additional boost immunizations with F1-V-MPR 649-684 recalled and maintained the antibody response and expanded the number of specific antibody-secreting B cells. Thus, while F1-V-MPR 649-684 alone was not sufficiently immunogenic to induce detectable levels of MPR 649-684-specific antibodies, these results suggest that prime-boost immunization using heterologous antigen-display platforms may overcome the poor humoral immunogenicity of MPR 649-684 for the induction of durable humoral immunity. Further studies are warranted to evaluate the feasibility of this strategy in mucosal immunization. Lastly, our findings add to a growing body of evidence in support of this strategy for immunogen design for poorly immunogenic epitopes besides the MPR of HIV-1's transmembrane envelope protein.",
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