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PMID: 7514676 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Protection against lethal lymphocytic choriomeningitis virus (LCMV) infection by immunization of mice with an influenza virus containing an LCMV epitope recognized by cytotoxic T lymphocytes.

Journal of virology ·Vol. 68 ·No. 6 ·1994-06-00 ·Pages 3486-90

Castrucci MR, Hou S, Doherty PC, Kawaoka Y

Abstract

The reverse genetics system has made it possible to modify the influenza virus genome. By this method, we were able to assess influenza virus as a vaccine vector for protecting BALB/c mice against otherwise lethal lymphocytic choriomeningitis virus (LCMV) infection. A single dose of influenza virus [A/WSN/33 (H1N1)] bearing a cytotoxic T-lymphocyte-specific epitope of the LCMV nucleoprotein (residues 116 to 127) in the neuraminidase stalk protected mice against LCMV challenge for at least 4 months. The immunity was mediated by cytotoxic T lymphocytes and was haplotype specific, indicating that the observed protective response was solely a consequence of prior priming with the H-2d LCMV nucleoprotein epitope expressed in the recombinant influenza virus. We also found that as many as 58 amino acids could be inserted into the neuraminidase stalk without loss of viral function. These findings demonstrate the potential of influenza virus as a vaccine vector, with the neuraminidase stalk as a repository for foreign epitopes.

MeSH Terms
Amino Acid Sequence Animals Epitopes/genetics Female Genetic Vectors Lymphocytic Choriomeningitis/prevention & control Lymphocytic choriomeningitis virus/genetics,immunology Mice Mice, Inbred BALB C Molecular Sequence Data Neuraminidase/genetics,immunology Orthomyxoviridae/genetics,immunology Recombination, Genetic T-Lymphocytes, Cytotoxic/immunology Vaccination Viral Vaccines/immunology
Chemicals
Epitopes Viral Vaccines Neuraminidase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Castrucci M R
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Hou S
Doherty P C
Kawaoka Y
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.68.6.3486-3490.1994
Published
1994-06-00
Pages
3486-90
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC236851
Subset
IM
Grants
NIAID NIH HHS · AI-29579 · United States
NIAID NIH HHS · AI-29599 · United States
NCI NIH HHS · CA-21765 · United States
External Links
PubMed source DOI: 10.1128/JVI.68.6.3486-3490.1994 PMC Full Text View journal details
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