• 1
    Verhoeyen, M., Fang, R., Min Jou, W., Devos, R., Huylebroeck, D., Saman, E., Fiers, W. (1980) Antigenic drift between the haemagglutinin of the Hong Kong influenza strains A/Aichi/2/68 and A/Victoria/3/75. Nature 286, 771 776.
  • 2
    Fang, R., Min Jou, W., Huylebroeck, D., Devos, R., Fiers, W. (1981) Complete structure of a/duck/Ukraine/63 influenza hemagglutinin gene: animal virus as progenitor of human H3: Hong Kong 1968 influenza hemagglutinin. Cell 25, 315 323.
  • 3
    Palese, P. & Young, J.F. (1982) Variation of influenza A, B, and C viruses. Science 215, 1468 1474.
  • 4
    Webster, R.G., Laver, W.G., Air, G.M., Schild, G.C. (1982) Molecular mechanisms of variation in influenza viruses. Nature 296, 115 121.
  • 5
    Schild, G.C., Oxford, J.S., De Jong, J.C., Webster, R.G. (1983) Evidence for host-cell selection of influenza virus antigenic variants. Nature 303, 706 709.
  • 6
    Robertson, J.S., Naeve, C.W., Webster, R.G., Bootman, J.S., Newman, R., Schild, G.C. (1985) Alterations in the hemagglutinin associated with adaptation of influenza B virus to growth in eggs. Virology 143, 166 174.
  • 7
    Katz, J.M., Naeve, C.W., Webster, R.G. (1987) Host cell mediated variation in H3N2 influenza viruses. Virology 156, 386 395.
  • 8
    Robertson, J.S., Cook, P., Nicolson, C., Newman, R., Wood, J.M. (1994) Mixed populations in influenza virus vaccine strains. Vaccine 12, 1317 1322.
  • 9
    Kodihalli, S., Justewicz, D.M., Gubareva, L.V., Webster, R.G. (1995) Selection of single amino acid substitution in the hemagglutinin molecule by chicken eggs can render influenza A virus (H3): Candidate Vaccine Ineffective. J. Virol. 69, 4888 4897.
  • 10
    Simeckova-Rosenberg, J., Yun, Z., Wyde, P.R., Atassi, M.Z. (1995) Protection of mice against lethal viral infection by synthetic peptides corresponding to B- and T-cell recognition sites of influenza A hemagglutinin. Vaccine 13, 927 932.
  • 11
    Ulmer, J.B., Donnelly, J.J., Parker, S.E., Rhodes, G.H., Felgner, P.L., Dwarki, V.J., Gromkowski, S.H., Deck, R.R., De Witt, C.M., Friedman, A., Hawe, L.A., Leander, K.R., Martinez, D., Perry, H.C., Shiver, J.W., Montgomery, D.L., Liu, M.A. (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259, 1745 1749.
  • 12
    Bender, B.S., Rowe, C.A., Taylor, S.F., Wyatt, L.S., Moss, B., Small, J.R. & P.A. (1996) Oral immunization with a replication-deficient recombinant vaccinia virus protects mice against influenza. J. Virol. 70, 6418 6424.
  • 13
    Rabinovich, N.R., McInnes, P., Klein, D.L., Hall, B.F. (1994) Vaccine technologies: view to the future. Science 265, 1401 1404.
  • 14
    Slepushkin, V.A., Katz, J.M., Black, R.A., Gamble, W.C., Rota, P.A., Cox, N.J. (1995) Protection of mice against influenza A virus challenge by vaccination with baculovirus-expressed M2 protein. Vaccine 13, 1399 1402.
  • 15
    Powers, D.C., Smith, G.E., Anderson, E.L., Kennedy, D.J., Hackett, C.S., Wilkinson, B.E., Volvovitz, F., Belshe, R.B., Treanor, J.J. (1995) Influenza A virus vaccines containing purified recombinant H3 hemagglutinin are well tolerated and induce protective immune responses in healthy adults. J. Infect. Dis. 171, 1595 1599.
  • 16
    Kilbourne, E.D., Couch, R.B., Kasel, J.A., Keitel, W.A., Cate, T.R., Quarles, J.H., Grajower, B., Pokorny, B.A., Johansson, B.E. (1995) Purified influenza A virus N2 neuraminidase vaccine is immunogenic and non-toxic in humans. Vaccine 13, 1799 1803.
  • 17
    Vanlandschoot, P., Maertens, G., Min Jou, W., Fiers, W. (1993) Recombinant secreted hemagglutinin protects mice against a lethal challenge of influenza virus. Vaccine 11, 1185 1187.
  • 18
    Deroo, T., Min Jou, W., Fiers, W. (1996) Recombinant neuraminidase vaccine protects against lethal influenza. Vaccine 14, 561 569.
  • 19
    White, J., Kartenbeck, J.S., Helenius, A. (1982) Membrane fusion activity of influenza virus. EMBO J. 1, 217 222.
  • 20
    Wiley, D.C. & Skehel, J.J. (1987) The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Ann.l Rev. Biochem. 56, 365 394.
  • 21
    Virelizier, J.-L. (1975) Host defences against influenza virus: the role of anti-hemagglutinin antibody. J. Immunol. 115, 434 439.
  • 22
    Kris, R.M., Yetter, R.A., Cogliano, R., Ramphal, R., Small, P.A. (1988) Passive serum antibody transfer causes temporary recovery from influenza virus infection of the nose, trachea and lung of nude mice. Immunology 63, 349 353.
  • 23
    Kida, H., Brown, L.E., Webster, R.G. (1982) Biological activity of monoclonal antibodies to operationally defined antigenic regions on the hemagglutinin molecule of A/Seal/Massachusetts/1/80 (H7N7) influenza virus. Virology 122, 38 47.
  • 24
    Kida, H., Yoden, S., Kuwabara, M., Yanagawa, R. (1985) Interference with a conformational change in the haemagglutinin molecule of influenza virus by antibodies as a possible neutralization mechanism. Vaccine 3, 219 222.
  • 25
    Klenk, H.-D., Rott, R., Orlich, M., Blodorn, J. (1975) Activation of influenza A virus by trypsin treatment. Virology 68, 426 439.
  • 26
    Lazarowitz, S.G. & Choppin, P.W. (1975) Enhancement of the infectivity of influenza A and B virus by proteolytic cleavage of the hemagglutinin polypeptide. Virology 68, 440 454.
  • 27
    Skehel, J.J. & Waterfield, M.D. (1982) Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion. Proc. Natl Acad. Sci. USA 79, 968 972.
  • 28
    Singh, I., Doms, R.W., Wagner, K.R., Helenius, A. (1990) Intracellular transport of soluble and membrane-bound glycoproteins: folding, assembly and secretion of anchor-free influenza hemagglutinin. EMBO J. 9, 631 639.
  • 29
    Martinet, W., Saelens, X., Deroo, T., Neirynck, S., Contreras, R., Min Jou, W., Fiers, W. (1997) Protection of mice against a lethal influenza challenge by immunization with yeast-derived recombinant influenza neuraminidase. Eur. J. Biochem. 247, 332 338.
  • 30
    Huylebroeck, D., Maertens, G., Verhoeyen, M., Lopez, C., Raeymakers, A., Min Jou, W., Fiers, W. (1988) High-level transient expression of influenza virus proteins from a series of SV40 late and early replacement vectors. Gene 66, 163 181.
  • 31
    Morinaga, Y., Franceschini, T., Inouye, S., Inouye, M. (1984) Improvement of oligonucleotide-directed site-specific mutagenesis using double-stranded plasmid DNA. Biotechnology 2, 636 639.
  • 32
    Norrander, J., Kempe, T., Messing, J. (1983) Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene 26, 101 106.
  • 33
    Min Jou, W., Verhoeyen, M., Devos, R., Saman, R., Fang, R., Huylebroeck, D., Fiers, W. (1980) Complete structure of the hemagglutinin gene from the human influenza A/Victoria/3/75 (H3N2) strain as determined from cloned DNA. Cell 19, 683 696.
  • 34
    Vanlandschoot, P., Beirnaert, E., Neirynck, S., Saelens, X., Min Jou, W., Fiers, W. (1996) Molecular and immunological charachterization of soluble aggregated A/Victoria/3/75 (H3N2) influenza haemagglutinin expressed in insect cells. Arch. Virol. 141, 1715 1726.
  • 35
    Morrissey, J.H. (1981) Silver stain for proteins in polyacrylamide gels: a modified procedure with enhanced uniform sensitivity. Anal. Biochem. 117, 307 310.
  • 36
    Bradford, M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248 254.
  • 37
    Jackson, P. (1994) The analysis of fluorophore-labeled glycans by high-resolution polyacrylamide gel electrophoresis. Anal. Biochem. 216, 243 252.
  • 38
    Russ, G., Polakova, K., Kostolansky, F., Styk, B., Vancikova, M. (1987) Monoclonal antibodies to glycopeptides HA1 and HA2 haemagglutinin subunits. Acta Virologica 31, 374 386.
  • 39
    Kostolansky, F., Russ, G., Mucha, V., Styck, B. (1988) Changes in the influenza virus hemagglutinin at acid pH detected by monoclonal antibodies to glycopolypeptides HA1 and HA2, Arch. Virol. 101, 13 24.
  • 40
    Wharton, S.A., Calder, L.J., Ruigrok, R.W.H., Skehel, J.J., Steinhauer, D.A., Wiley, D.C. (1995) Electron microscopy of antibody complexes of influenza virus hemagglutinin in the fusion pH conformation. EMBO J. 14, 240 246.
  • 41
    Vanlandschoot, P., Beirnaert, E., Dewilde, S., Saelens, X., Bestebroer, T., Min Jou, W., Fiers, W. (1995) A fairly conserved epitope on the hemagglutinin of influenza A (H3N2) virus with variable accessibility to neutralizing antibody. Virology 212, 526 534.
  • 42
    Vanlandschoot, P., Beirnaert, E., Barrère, B., Calder, L., Millar, B., Wharton, S., Min Jou, W., Fiers, W. (1998) An antibody which binds to the membrane-proximal end of influenza virus haemagglutinin (H3 subtype) inhibits the low-pH-induced conformational change and cell-cell fusion but does not neutralize virus. J. Gen. Virol. 79, 1781 1791.
  • 43
    Vanlandschoot, P., Beirnaert, E., Grooten, J., Min Jou, W., Fiers, W. (1998) pH-dependent aggregation and secretion of soluble monomeric influenza hemagglutinin. Arch. Virol. 143, 227 239.
  • 44
    Tschopp, J.F., Sverlow, G., Kosson, R., Craig, W., Grinna, L. (1987) High-level secretion of glycosylated invertase in the methylotrophic yeast, Pichia pastoris. Biotechnology 5, 1305 1308.
  • 45
    Grinna, L.S. & Tschopp, J.F. (1989) Size distribution and general structural features of N-linked oligosaccharides form the methylotrophic yeast, Picha pastoris. Yeast 5, 107 115.
  • 46
    Cregg, J.M., Vedvick, T.S., Raschke, W.C. (1993) Recent advances in the expression of foreign genes in Pichia pastoris. Biotechnology 11, 905 910.
  • 47
    Romanos, M.A., Scorer, C.A., Clare, J.J. (1992) Foreign gene expression in yeast: a review. Yeast 8, 423 488.
  • 48
    Jabbar, M.A. & Nayak, D.P. (1987) Signal processing, glycosylation, and secretion of mutant hemagglutinins of a human influenza virus by Saccharomyces cerevisiae. Mol. Cell. Biol. 7, 1476 1485.
  • 49
    Matlin, K.S., Skibbens, J., McNeil, P.C. (1988) Reduced extracellular pH reversibly inhibits oligomerization, intracellular transport, and processing of the influenza hemagglutinin in infected Madin-Darby Canine Kidney cells. J. Biol. Chem. 263, 11478 11485.
  • 50
    Gabrielsen, O.S., Reppe, S., Saether, O., Blingsmo, O.R., Sletten, K., Gordeladze, J.O., Hogset, A., Gautvik, V.T., Alestrom, P., Oyen, T.B., T.B., Gautvik, K.M. (1990) Efficient secretion of human parathyroid hormone by Saccharomyces Cerevisiae. Gene 90, 255 262.
  • 51
    Zsebo, K.M., Lu, H.-S., Fieschko, J.C., Goldstein, L., Davis, J., Dukker, K., Suggs, S.V., Lai, P.-H., Bitter, G.A. (1986) Protein secretion from Saccharomyces cerevisiae directed by the prepro-α-factor leader region. J. Biol. Chem. 261, 5858 5865.
  • 52
    Ulrich, J.T. & Myers, K.R. (1995) Monophosphoryl lipid A as an adjuvant. Past experiences and new directions. Pharm. Biotechnol. 6, 495 524.
  • 53
    Thoelen, S., Van Damme, P., Mathei, C., Leroux-Roels, G., Desombere, I., Safary, A., Vandepapeliere, P., Slaoui, M., Meheus, A. (1998) Safety and immunogenicity of a hepatitis B vaccine formulated with a novel adjuvant system. Vaccine 7, 708 714.
  • 54
    Kuroda, K., Hauser, C., Rott, R., Klenk, H.-D., Doerfler, W. (1986) Expression of the influenza virus haemagglutinin in insect cells by a baculovirus vector. EMBO J. 5, 1359 1365.
  • 55
    Subbarao, K., Klimov, A., Katz, J., Regnery, H., Lim, W., Hall, H., Perdue, M., Swayne, D., Bender, C., Huang, J., Hemphill, M., Rowe, T., Shaw, M., Xu, X., Fukuda, K., Cox, N. (1998) Characterization of an avian influenza A (H5N1) virus Isolated from a child with a fatal respiratory illness, Science 279, 393 396.
  • 56
    Pennisi, E. (1995) Planning for the next flu pandemic. Nature 270, 1916 1917.
  • 57
    Jack, D.B. (1996) Getting ready for the next influenza pandemic. Lancet 347, 1252.