ABSTRACT
The immunogenicity and toxicity of a purified influenza virus (N2) neuraminidase vaccine (NAV) were investigated in 88 human subjects aged 18-40, and compared to response to a conventional trivalent influenza vaccine, Fluogen (Parke-Davis). NAV doses ranged from 2.6 to 69.9 micrograms and were given intramuscularly. Serologic neuraminidase-inhibiting (NI) and neuraminidase-specific ELISA responses in this N2-primed population were roughly proportional to the dose administered. Maximal response was seen in 14-21 days and NI antibody titers persisted unabated for the 6-month post-vaccination follow-up period. All doses were well tolerated with respect to local and systemic reactions. NI tests performed with the putative (1975) priming N2 antigen demonstrated anamnestic response but did not reveal responses not already shown with the homologous (1992) antigen. Response to this purified, non-adjuvanted preparation encourages continuing investigation of the induction of infection-permissive immunity with influenza virus neuraminidase.
Subject(s)
Influenza A virus/immunology , Influenza Vaccines/immunology , Neuraminidase/immunology , Adolescent , Adult , Antibody Formation , Antibody Specificity , Chromatography, Affinity , Humans , Influenza Vaccines/adverse effectsABSTRACT
Genetic reassortment of the A/Shanghai/11/87 (H3N2) variant of influenza A virus with A/PR8/34 (H1N1) virus [the standard donor of high yield (hy) genes for influenza vaccine viruses] resulted in the isolation of two reassortants with differing H3 haemagglutinin (HA) phenotypes, X-99 and X-99a. The two HA phenotypes were derived from individual subpopulations of the H3N2 wild-type virus during the reassortment event. The HA mutants and their respectively derived reassortants (identical in RNA genotype) differed in antigenicity, replication characteristics, yield in chick embryos and haemagglutinin gene sequence. Despite antigenic differences in reactions to polyclonal rabbit antisera of 60%, both X-99 and X-99a, the hy reassortants, were equally immunogenic and protective in BALB/c mice to challenge by parental wild-type virus. Differences in HA phenotype were related to a Ser to Ile change at amino acid position 186. These findings emphasize the polymorphism of influenza virus strains as well as the need for caution in selection of vaccine strains from among antigenically distinct viral subpopulations.
Subject(s)
Hemagglutinins, Viral/immunology , Influenza A Virus, H3N2 Subtype , Influenza A virus/genetics , Polymorphism, Genetic , Amino Acid Sequence , Animals , Base Sequence , Chick Embryo , Female , Genetic Variation , Genotype , Hemagglutination Inhibition Tests , Hemagglutinin Glycoproteins, Influenza Virus , Hemagglutinins, Viral/genetics , Influenza A virus/immunology , Mice , Mice, Inbred BALB C/immunology , Molecular Sequence Data , Neutralization Tests , Oligodeoxyribonucleotides , Phenotype , RNA, Viral/genetics , RNA, Viral/isolation & purification , Rabbits/immunology , Viral Envelope Proteins/immunologyABSTRACT
A panel of monoclonal antibodies to the M1 protein of A/PR8/34 (H1N1) (PR8) influenza A virus was found to distinguish in ELISA high-yielding reassortant viruses derived from reassortment of PR8 and X-31 (H3N2) viruses with recently prevalent field strains of H1N1 or H3N2 subtype. These findings are concordant with results of genotyping that demonstrated the presence of PR8 RNA 7 or M1 protein in high-yield reassortants by RNA or protein PAGE. All high-yield vaccine candidate reassortants Application of the M1 monoclonal antibody panel facilitates the isolation of high-yield vaccine candidate reassortants bearing the PR8 M1 gene, and should aid in epidemiologic strain tracking as well.
