Beta 2-microglobulin-deficient mice can be protected against influenza A infection by vaccination with vaccinia-influenza recombinants expressing hemagglutinin and neuraminidase.
Immunity to viral infections includes both antibody and T cell components. The contributions of humoral and cell-mediated immune responses vary depending on virus and host factors. We have used an in vivo challenge system to examine protective immunity to influenza A(H1N1) virus infection in immunocompetent B6 (H-2b) mice, and in H-2b mice homozygous for disruption of the gene for beta 2-microglobulin, termed beta 2 mu(-/-) mice. The latter mice do not express conventional MHC class I complexes on cell surfaces and lack CD8+ class I-restricted T cells. Ten vaccinia virus recombinants, each expressing 1 of the 10 proteins of influenza virus, were used to immunize the mice. Normal mice were protected against challenge with influenza virus by vaccination with HA-VAC and NA-VAC, but not by any of the vaccinia vectors expressing one of the eight other influenza virus proteins nor by a mixture of all eight of the latter vectors. Similar results were observed in mice of H-2d or H-2k MHC haplotypes. The beta 2 mu(-/-) mice were also protected by immunization with HA-VAC and NA-VAC, demonstrating that classical CD8+ CTL responses were not required for protection. Depletion of CD4+ T cells in either normal or beta 2 mu(-/-) mice at the time of challenge had little or no effect on protection induced by HA-VAC or NA-VAC, suggesting that preformed antibody is the dominant mediator of protective immunity induced by these recombinants. Antibody responses to vaccinia virus Ag and expressed influenza virus Ag were lower in titer in beta 2 mu(-/-) mice than in normal B6 mice, suggesting an influence of MHC class I complexes, CD8+ T cells, or their products on antibody production.
Molecular Immunology Laboratory, Food and Drug Administration, Bethesda, MD 20892.
S L
SL
Epstein
J A
JA
Misplon
C M
CM
Lawson
E K
EK
Subbarao
M
M
Connors
B R
BR
Murphy
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D006183:H-2 Antigens / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency*
D000914:Antibodies, Viral; D006183:H-2 Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D001613:beta 2-Microglobulin; D009439:Neuraminidase