A hemagglutinin-based multipeptide construct elicits enhanced protective immune response in mice against influenza A virus infection

A. Horváth, G. Tóth, P. Gogolák, Zoltán Nagy, Istaván Kurucz, Israel Pecht, E. Rajnavolgyi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Multipeptide constructs, comprising adjacent sequences of the 317-341 intersubunit region of immature influenza A hemagglutinin (H1N1), were designed and the functional properties of these branched peptides were compared to that of the corresponding linear peptides. In vivo studies revealed that the immunogenicity of the peptides was dependent on the presence of the hydrophobic fusion peptide (comprised in FP3), encompassing the N-terminal 1-13 sequence of the HA2 subunit. Antibody and T cell recognition, however, was directed against the 317-329 HA1 sequence, comprised in the P4 peptide. Multiple copies of P4, covalently linked by branched lysine residues, significantly enhanced the efficiency of antibody binding and the capacity of peptides to elicit B- and T-cell responses. A fraction of peptide induced antibodies reacted with immature or with proteolitically cleaved hemagglutinin (HA) molecules pretreated at low pH. Immunization with a multipeptide construct, (P4)4-FP3, not only resulted in elevated antibody and T cell responses but conferred enhanced protection against lethal A/PR/8/34 (H1N1) infection as compared to its subunit peptides. The beneficial functional properties of this artificial peptide antigen may be acquired by multiple properties including: (i) stabilized peptide conformation which promotes strong, polyvalent binding to both antibodies and MHC class II molecules; (ii) appropriate P4 conformation for antibody recognition stabilized by the covalently coupled fusion peptide, resulting in the production of virus cross reactive antibodies which inhibit the fusion activity of the virus; (iii) activation of peptide specific B cells which potentiate antigen presentation and peptide specific T cell responses; and (iv) generation of helper T cells which secrete lymphokines active in the resolution of infection.

Original languageEnglish
Pages (from-to)127-136
Number of pages10
JournalImmunology Letters
Volume60
Issue number2-3
DOIs
Publication statusPublished - Feb 1998

Fingerprint

Influenza A virus
Hemagglutinins
Virus Diseases
Peptides
Antibodies
T-Lymphocytes
Viruses
Peptide T
Immunoglobulin Isotypes
Lymphokines
Antigen Presentation
Helper-Inducer T-Lymphocytes
Infection
Human Influenza
Lysine
Immunization
B-Lymphocytes
Antigens

Keywords

  • Hemagglutinin
  • Immune response
  • Influenza A virus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

A hemagglutinin-based multipeptide construct elicits enhanced protective immune response in mice against influenza A virus infection. / Horváth, A.; Tóth, G.; Gogolák, P.; Nagy, Zoltán; Kurucz, Istaván; Pecht, Israel; Rajnavolgyi, E.

In: Immunology Letters, Vol. 60, No. 2-3, 02.1998, p. 127-136.

Research output: Contribution to journalArticle

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