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.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahmed R., Byrne J. A., Oldstone M. B. Virus specificity of cytotoxic T lymphocytes generated during acute lymphocytic choriomeningitis virus infection: role of the H-2 region in determining cross-reactivity for different lymphocytic choriomeningitis virus strains. J Virol. 1984 Jul;51(1):34–41. doi: 10.1128/jvi.51.1.34-41.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allan J. E., Doherty P. C. Consequences of a single Ir-gene defect for the pathogenesis of lymphocytic choriomeningitis. Immunogenetics. 1985;21(6):581–589. doi: 10.1007/BF00395882. [DOI] [PubMed] [Google Scholar]
- Allan W., Tabi Z., Cleary A., Doherty P. C. Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T cells. J Immunol. 1990 May 15;144(10):3980–3986. [PubMed] [Google Scholar]
- Brutkiewicz R. R., Klaus S. J., Welsh R. M. Window of vulnerability of vaccinia virus-infected cells to natural killer (NK) cell-mediated cytolysis correlates with enhanced NK cell triggering and is concomitant with a decrease in H-2 class I antigen expression. Nat Immun. 1992 Jul-Aug;11(4):203–214. [PubMed] [Google Scholar]
- Byrne J. A., Oldstone M. B. Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo. J Virol. 1984 Sep;51(3):682–686. doi: 10.1128/jvi.51.3.682-686.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Castrucci M. R., Kawaoka Y. Biologic importance of neuraminidase stalk length in influenza A virus. J Virol. 1993 Feb;67(2):759–764. doi: 10.1128/jvi.67.2.759-764.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cserr H. F., Knopf P. M. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today. 1992 Dec;13(12):507–512. doi: 10.1016/0167-5699(92)90027-5. [DOI] [PubMed] [Google Scholar]
- Del Val M., Schlicht H. J., Volkmer H., Messerle M., Reddehase M. J., Koszinowski U. H. Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope. J Virol. 1991 Jul;65(7):3641–3646. doi: 10.1128/jvi.65.7.3641-3646.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dewar R. L., Natarajan V., Vasudevachari M. B., Salzman N. P. Synthesis and processing of human immunodeficiency virus type 1 envelope proteins encoded by a recombinant human adenovirus. J Virol. 1989 Jan;63(1):129–136. doi: 10.1128/jvi.63.1.129-136.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doherty P. C., Allan W., Eichelberger M., Carding S. R. Roles of alpha beta and gamma delta T cell subsets in viral immunity. Annu Rev Immunol. 1992;10:123–151. doi: 10.1146/annurev.iy.10.040192.001011. [DOI] [PubMed] [Google Scholar]
- Doherty P. C., Zinkernagel R. M. T-cell-mediated immunopathology in viral infections. Transplant Rev. 1974;19(0):89–120. doi: 10.1111/j.1600-065x.1974.tb00129.x. [DOI] [PubMed] [Google Scholar]
- Dutko F. J., Oldstone M. B. Genomic and biological variation among commonly used lymphocytic choriomeningitis virus strains. J Gen Virol. 1983 Aug;64(Pt 8):1689–1698. doi: 10.1099/0022-1317-64-8-1689. [DOI] [PubMed] [Google Scholar]
- Enami M., Luytjes W., Krystal M., Palese P. Introduction of site-specific mutations into the genome of influenza virus. Proc Natl Acad Sci U S A. 1990 May;87(10):3802–3805. doi: 10.1073/pnas.87.10.3802. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Enami M., Palese P. High-efficiency formation of influenza virus transfectants. J Virol. 1991 May;65(5):2711–2713. doi: 10.1128/jvi.65.5.2711-2713.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Enami M., Sharma G., Benham C., Palese P. An influenza virus containing nine different RNA segments. Virology. 1991 Nov;185(1):291–298. doi: 10.1016/0042-6822(91)90776-8. [DOI] [PubMed] [Google Scholar]
- Evans D. J., McKeating J., Meredith J. M., Burke K. L., Katrak K., John A., Ferguson M., Minor P. D., Weiss R. A., Almond J. W. An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies. Nature. 1989 Jun 1;339(6223):385-8, 340. doi: 10.1038/339385a0. [DOI] [PubMed] [Google Scholar]
- Itamura S., Iinuma H., Shida H., Morikawa Y., Nerome K., Oya A. Characterization of antibody and cytotoxic T lymphocyte responses to human influenza virus H3 haemagglutinin expressed from the haemagglutinin locus of vaccinia virus. J Gen Virol. 1990 Dec;71(Pt 12):2859–2865. doi: 10.1099/0022-1317-71-12-2859. [DOI] [PubMed] [Google Scholar]
- Jenkins O., Cason J., Burke K. L., Lunney D., Gillen A., Patel D., McCance D. J., Almond J. W. An antigen chimera of poliovirus induces antibodies against human papillomavirus type 16. J Virol. 1990 Mar;64(3):1201–1206. doi: 10.1128/jvi.64.3.1201-1206.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kast W. M., Roux L., Curren J., Blom H. J., Voordouw A. C., Meloen R. H., Kolakofsky D., Melief C. J. Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with a free synthetic peptide. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2283–2287. doi: 10.1073/pnas.88.6.2283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kieny M. P., Lathe R., Drillien R., Spehner D., Skory S., Schmitt D., Wiktor T., Koprowski H., Lecocq J. P. Expression of rabies virus glycoprotein from a recombinant vaccinia virus. Nature. 1984 Nov 8;312(5990):163–166. doi: 10.1038/312163a0. [DOI] [PubMed] [Google Scholar]
- Klavinskis L. S., Whitton J. L., Oldstone M. B. Molecularly engineered vaccine which expresses an immunodominant T-cell epitope induces cytotoxic T lymphocytes that confer protection from lethal virus infection. J Virol. 1989 Oct;63(10):4311–4316. doi: 10.1128/jvi.63.10.4311-4316.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kunkel T. A., Roberts J. D., Zakour R. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987;154:367–382. doi: 10.1016/0076-6879(87)54085-x. [DOI] [PubMed] [Google Scholar]
- Lehmann-Grube F., Moskophidis D., Löhler J. Recovery from acute virus infection. Role of cytotoxic T lymphocytes in the elimination of lymphocytic choriomeningitis virus from spleens of mice. Ann N Y Acad Sci. 1988;532:238–256. doi: 10.1111/j.1749-6632.1988.tb36343.x. [DOI] [PubMed] [Google Scholar]
- Li S. Q., Schulman J. L., Moran T., Bona C., Palese P. Influenza A virus transfectants with chimeric hemagglutinins containing epitopes from different subtypes. J Virol. 1992 Jan;66(1):399–404. doi: 10.1128/jvi.66.1.399-404.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li S., Polonis V., Isobe H., Zaghouani H., Guinea R., Moran T., Bona C., Palese P. Chimeric influenza virus induces neutralizing antibodies and cytotoxic T cells against human immunodeficiency virus type 1. J Virol. 1993 Nov;67(11):6659–6666. doi: 10.1128/jvi.67.11.6659-6666.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li S., Rodrigues M., Rodriguez D., Rodriguez J. R., Esteban M., Palese P., Nussenzweig R. S., Zavala F. Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5214–5218. doi: 10.1073/pnas.90.11.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lin Y. L., Askonas B. A. Biological properties of an influenza A virus-specific killer T cell clone. Inhibition of virus replication in vivo and induction of delayed-type hypersensitivity reactions. J Exp Med. 1981 Aug 1;154(2):225–234. doi: 10.1084/jem.154.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lukacher A. E., Braciale V. L., Braciale T. J. In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. J Exp Med. 1984 Sep 1;160(3):814–826. doi: 10.1084/jem.160.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luo G., Chung J., Palese P. Alterations of the stalk of the influenza virus neuraminidase: deletions and insertions. Virus Res. 1993 Aug;29(2):141–153. doi: 10.1016/0168-1702(93)90055-r. [DOI] [PubMed] [Google Scholar]
- Luytjes W., Krystal M., Enami M., Parvin J. D., Palese P. Amplification, expression, and packaging of foreign gene by influenza virus. Cell. 1989 Dec 22;59(6):1107–1113. doi: 10.1016/0092-8674(89)90766-6. [DOI] [PubMed] [Google Scholar]
- Lynch F., Doherty P. C., Ceredig R. Phenotypic and functional analysis of the cellular response in regional lymphoid tissue during an acute virus infection. J Immunol. 1989 May 15;142(10):3592–3598. [PubMed] [Google Scholar]
- Mackett M., Yilma T., Rose J. K., Moss B. Vaccinia virus recombinants: expression of VSV genes and protective immunization of mice and cattle. Science. 1985 Jan 25;227(4685):433–435. doi: 10.1126/science.2981435. [DOI] [PubMed] [Google Scholar]
- Morin J. E., Lubeck M. D., Barton J. E., Conley A. J., Davis A. R., Hung P. P. Recombinant adenovirus induces antibody response to hepatitis B virus surface antigen in hamsters. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4626–4630. doi: 10.1073/pnas.84.13.4626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moss B. Vaccinia virus: a tool for research and vaccine development. Science. 1991 Jun 21;252(5013):1662–1667. doi: 10.1126/science.2047875. [DOI] [PubMed] [Google Scholar]
- Murray M. G., Kuhn R. J., Arita M., Kawamura N., Nomoto A., Wimmer E. Poliovirus type 1/type 3 antigenic hybrid virus constructed in vitro elicits type 1 and type 3 neutralizing antibodies in rabbits and monkeys. Proc Natl Acad Sci U S A. 1988 May;85(9):3203–3207. doi: 10.1073/pnas.85.9.3203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oldstone M. B., Tishon A., Geckeler R., Lewicki H., Whitton J. L. A common antiviral cytotoxic T-lymphocyte epitope for diverse major histocompatibility complex haplotypes: implications for vaccination. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2752–2755. doi: 10.1073/pnas.89.7.2752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paoletti E., Lipinskas B. R., Samsonoff C., Mercer S., Panicali D. Construction of live vaccines using genetically engineered poxviruses: biological activity of vaccinia virus recombinants expressing the hepatitis B virus surface antigen and the herpes simplex virus glycoprotein D. Proc Natl Acad Sci U S A. 1984 Jan;81(1):193–197. doi: 10.1073/pnas.81.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prickett K. S., Amberg D. C., Hopp T. P. A calcium-dependent antibody for identification and purification of recombinant proteins. Biotechniques. 1989 Jun;7(6):580–589. [PubMed] [Google Scholar]
- Smith G. L., Murphy B. R., Moss B. Construction and characterization of an infectious vaccinia virus recombinant that expresses the influenza hemagglutinin gene and induces resistance to influenza virus infection in hamsters. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7155–7159. doi: 10.1073/pnas.80.23.7155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sugiura A., Ueda M. Neurovirulence of influenza virus in mice. I. Neurovirulence of recombinants between virulent and avirulent virus strains. Virology. 1980 Mar;101(2):440–449. doi: 10.1016/0042-6822(80)90457-2. [DOI] [PubMed] [Google Scholar]
- Taylor P. M., Askonas B. A. Diversity in the biological properties of anti-influenza cytotoxic T cell clones. Eur J Immunol. 1983 Sep;13(9):707–711. doi: 10.1002/eji.1830130904. [DOI] [PubMed] [Google Scholar]
- Taylor P. M., Davey J., Howland K., Rothbard J. B., Askonas B. A. Class I MHC molecules rather than other mouse genes dictate influenza epitope recognition by cytotoxic T cells. Immunogenetics. 1987;26(4-5):267–272. doi: 10.1007/BF00346521. [DOI] [PubMed] [Google Scholar]
- Welsh R. M., Jr, Zinkernagel R. M., Hallenbeck L. A. Cytotoxic cells induced during lymphocytic choriomeningitis virus infection of mice. II. "Specificities" of the natural killer cells. J Immunol. 1979 Feb;122(2):475–481. [PubMed] [Google Scholar]
- Whitton J. L., Sheng N., Oldstone M. B., McKee T. A. A "string-of-beads" vaccine, comprising linked minigenes, confers protection from lethal-dose virus challenge. J Virol. 1993 Jan;67(1):348–352. doi: 10.1128/jvi.67.1.348-352.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whitton J. L., Southern P. J., Oldstone M. B. Analyses of the cytotoxic T lymphocyte responses to glycoprotein and nucleoprotein components of lymphocytic choriomeningitis virus. Virology. 1988 Feb;162(2):321–327. doi: 10.1016/0042-6822(88)90471-0. [DOI] [PubMed] [Google Scholar]
- Whitton J. L., Tishon A., Lewicki H., Gebhard J., Cook T., Salvato M., Joly E., Oldstone M. B. Molecular analyses of a five-amino-acid cytotoxic T-lymphocyte (CTL) epitope: an immunodominant region which induces nonreciprocal CTL cross-reactivity. J Virol. 1989 Oct;63(10):4303–4310. doi: 10.1128/jvi.63.10.4303-4310.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wysocka M., Hackett C. J. Class I H-2d-restricted cytotoxic T lymphocytes recognize the neuraminidase glycoprotein of influenza virus subtype N1. J Virol. 1990 Mar;64(3):1028–1032. doi: 10.1128/jvi.64.3.1028-1032.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]