Antigenic and amino acid sequence analysis of the variants of H1N1 influenza virus in 1986

Since their reintroduction to human populations in 1977, influenza A viruses of the H1N1 subtype have undergone antigenic drift. Recently a distinct antigenic variant, A/Singapore/6/86, has been almost exclusively isolated internationally, and the antigenic properties and amino acid sequence of its haemagglutinin have been determined and compared with those of the haemagglutinins of other H1N1 viruses, in particular A/Chile/1/83. Fourteen amino acid sequence differences are detected between the HA1 components of these two viruses, ten of which are different from equivalent residues in the haemagglutinins of all H1N1 viruses isolated between 1982 and 1983, and seven of which are novel in the haemagglutinins of all H1N1 viruses sequenced to date. The results are discussed in relation to the three-dimensional structure of the haemagglutinin and the location of the previously defined antigenically important regions.     

Frequency of naturally occurring antibody to influenza virus antigenic variants selected in vitro with monoclonal antibody.

Antigenic variants of A/Texas/77 (H3N2) virus were selected in vitro using monoclonal antibody to virus haemagglutinin (HA). The antigenic variants and parental A/Texas/77 viruses were used to to evaluate the frequency of anti-HA antibodies in the sera of children and adults using single-radial-haemolysis (SRH) tests. Twenty to 41% of selected sera from adults, which contained antibody to the parental A/Texas/77 virus, failed to react with the different antigenic mutant viruses. A higher proportion of sera from children (37-58%) failed to react with the antigenic variants. Certain human sera and particularly those of children would appear to possess a more limited antibody repertoire to influenza HA, potentially allowing new antigenic variants to escape neutralization and spread in the community.     

Antigenic relationships between the neuraminidases of influenza B virus

Antigenic relationships between neuraminidases of influenza B viruses isolated from 1940 to 1968 were studied by neuraminidase-inhibition tests using hyperimmune rabbit antisera. The cross-reactions between the enzymes of influenza B viruses showed that some antigenic drift had occurred but that they are all related. From these results it is concluded that the differences between the neuraminidases of influenza B viruses are not sufficiently clear-cut to allow the viruses to be separated into subgroups.     

Antigenic heterogeneity within influenza A (H3N2) virus strains

On the basis of their antigenic properties, influenza virus strains are classified into types and subtypes, which are further subdivided into variants that differ to various degrees in haemagglutination-inhibition assays. Evidence is presented that during infection with an influenza A(H3N2) virus the respiratory tract of a human patient often harbours more than one antigenic virus variant. These variants are frequently propagated by embryonated fowl eggs and monkey cells with different efficiencies, and this may lead to the selection of different variants by either of these host systems. Also, passage of virus by a given host is sometimes attended by changes in reactivity in haemagglutination-inhibition tests. In some cases the heterogeneity described also affects the specific immunogenicity of the virus in ferrets. Virus strains cloned in monkey kidney cell cultures gave variants that were stable upon further passage. These results may have implications for antigenic and biochemical investigations of epidemiologically relevant virus variants. It is argued that the antigenic drift of influenza A(H3N2) viruses is best characterized by analyses, both with post-infection ferret antisera and with panels of monoclonal antibodies, of virus strains isolated and passaged in monkey kidney cell cultures only.     

Antigenic analysis of H2 influenza virus haemagglutinin with monoclonal antibodies

Antigenic analysis of human and avian H2 influenza virus was carried out with monoclonal antibodies to the HA molecules of H2 influenza viruses isolated in the early stage of an H2 pandemic. The study revealed antigenic differences between inhibitor sensitive (Japan⁺/57, RI⁺57) and inhibitor resistant strains (Japan^?/57, Ri^?/57). This indicates that the receptor-binding specificity of the haemagglutinin can markedly influence the antigenic analysis obtained with monoclonal antibodies in HI test. Minor antigenic differences (microheterogeneity) could be detected between different H2 influenza viruses isolated in 1957. Minor antigenic variation continued in the H2 viruses until 1961, but significant antigenic drift occurred in 1962 so that viruses isolated after that date reacted with few monoclonal antibodies. Analysis of avian H2 influenza viruses suggested antigenic differences between the different avian H2 haemagglutinin but no correlation between the year of isolation and the progressive antigenic drift similar to that seen in the human strains was found.     

Antigenic variation among avian influenza A viruses

A total of 16 strains of influenza A virus isolated in 1965-66 from quail, ducks, turkeys, pheasants and chickens bred in poultry farms situated in Pavia and surrounding districts in northern Italy were investigated from the point of view of antigenic grouping by the complement-fixation test.     

Antigenic variation in current human type A influenza viruses: antigenic characteristics of the variants and their geographic distribution

Outbreaks of influenza due to the virus A/Hong Kong/1/68 (H3N2) began in 1968 and are still occurring. The haemagglutinin of this virus is different from that of the A/Singapore/1/57 virus (the “Asian” strain) but the neuraminidase antigens are the same. Between 1968 and 1971 only minor antigenic “drift” in the haemagglutinin was noted, but in recent months 2 isolates have been identified in which considerable “drift” has occurred in the haemagglutinin and in the neuraminidase antigens. One, A/Hong Kong/5/72 (H3N2), was first detected in outbreaks in Hong Kong between November 1971 and January 1972 and was predominant there and in Korea but did not become widely disseminated. The second strain, A/England/42/72 (H3N2), has been isolated in winter outbreaks in the southern hemisphere and now appears to be the predominant strain in the northern hemisphere. The characteristics of the strains are described.     

Antigenic properties and protective capacity of a cyclic peptide corresponding to site A of influenza virus haemagglutinin

Two cyclic peptide analogues corresponding to residues 139-146 (site A) of influenza A virus haemagglutinin (strain X31) were synthesized. The ability of these peptides to react with anti-influenza virus antibodies was found to depend on the conformation of the loop and on the orientation in which the peptide was presented to antibodies. Antibodies raised to the peptides were able to bind in ELISA with influenza virus antigen that had been allowed to dry on the microtitre plate. When OF1 mice were immunized with cyclic peptides, approximately 80% of the animals were protected against an intranasal challenge with influenza virus.     

Studies on the cultivation of influenza virus in vitro

Studies have been carried out since 1959 at the Coonoor Influenza Centre to devise a method of cultivating influenza virus in vitro which would be suitable for large-scale virus production. The authors report the successful cultivation of the virus in tissue cultures of chorioallantoic membrane on glass wool. The method described may be used equally satisfactorily for culture in volumes ranging from 1.0 ml to 350 ml, and is as sensitive as cultivation in eggs for the titration of different strains of influenza virus and their neutralizing antibodies. Relatively pure virus for vaccine production and complement-fixing antigen for diagnostic purposes can be produced in large volumes with ease and economy.     

溶葡萄球菌复合酶体外抗流感病毒效果研究

目的：研究溶葡萄球菌复合酶体外抗流感病毒效果，探寻预防、治疗流感病毒感染的新药和给药途径。方法：应用细胞病变抑制试验和直接免疫荧光法．经不同给药途径、作用时间和剂量，研究溶葡萄球菌复合酶体外抗流感病毒效果。并与已被普遍公认有效的抗流感药物磷酸奥司他韦比较。结果：两种试验方法都显示，两种药物在不同给药方式下，大部分实验组对病毒的抑制作用与对照组相比均有统计学意义（P〈0．05）。溶葡萄球菌复合酶1：5稀释后与病毒作用30min和磷酸奥司他韦治疗组的抗病毒效果最显著，且两者间差别无统计学意义（P〉0．05）。结论：溶葡萄球菌复合酶在体外抗流感病毒中具有较明显的作用，部分实验组的效果和公认的高效抗流感药物磷酸奥司他韦没有差别。在预防流感流行中具有一定的应用前景。