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Biomedical subjects

A S Beare

Publications and source records attributed to A S Beare.

53 records · Page 3Linked to original sources
PubMed1971

Neuraminidase and resistance to vaccination with live influenza A2 Hong Kong vaccines.

Thirty-seven volunteers were inoculated intranasally with living attenuated influenza A2 viruses. Rising titres of circulating antineuraminidase (AN) were detected in 14 of 17 infected volunteers. AN was also found in nasal secretions. Statistical analysis showed that there was a correlation between the titres of haemagglutination-inhibiting antibody (HI) and AN in nasal washings, and between AN in blood and washings. Resistance to infection could be predicted from antibody titres in 29 of 37 volunteers and blood AN alone predicted the outcome of 25 volunteers.

Antibodies↗
PubMed1971

A comparative study of attenuated influenza viruses.

Influenza A and influenza B viruses were adapted to growth at 25 degrees C. When given to volunteer subjects, the viruses were attenuated but remained infective and antigenic. The minimum immunizing dose of an egg-adapted virus appeared to be 10(5.0) EID(50). Cloning by plaque selection at 25 degrees C gave seed cultures of relatively low infectivity titres. These titres were increased when necessary by passage at 33 degrees C. No reversion to virulence was observed.Viruses attenuated in the United Kingdom and the USA were compared in volunteer trials with vaccine strains that had already been used in the USSR for mass immunization. Results were broadly similar. Currently available methods of attenuation and work with temperature-sensitive mutants are reviewed.

England↗
PubMed1969

Attenuation of human influenza A viruses.

The attenuation of two human influenza A viruses has been carried out, using the selection of inhibitor-resistant strains and multiple passages at low temperatures. A virus related to A2/Tokyo/3/67 was obtained in an inhibitor-resistant form. When this was compared with the inhibitor-sensitive strain in a volunteer trial it was relatively non-pathogenic. The second virus, A2/Hongkong/1/68, was subjected to much longer treatment, but nevertheless remained slightly sensitive to serum inhibitor. When given to volunteers it was less pathogenic than before but attenuation was incomplete. A2/Hongkong/1/68 was also modified by passage at low temperatures. Many of these passages are apparently necessary for full attenuation.All attenuated viruses were infective and antigenic.

Antibody Formation↗
PubMed1969

Antibody responses to and efficacy of an inactivated spray vaccine.

An attempt was made to assess the protective influence of killed intranasal influenza B vaccine against a homologous virus challenge. Two types of trial were performed. In the first of these, the vaccine was compared with an inert placebo and, in the second, with conventional homologous and heterologous parenteral vaccines. Little protective effect by the intranasal vaccine was demonstrated.

Adult↗
PubMed1969

Some studies on the selection and efficiency of live influenza vaccine viruses.

Live influenza virus vaccination has potential advantages and disadvantages compared with killed virus vaccine given by intramuscular injection.Attempts have been made to achieve complete attenuation of influenza A2 and B strains by up to 30 serial passages in the allantoic cavity of eggs at 33 degrees C. No attenuation occurred. The method of passing viruses in the presence of an increasing concentration of horse serum, thus selecting inhibitor-resistant variants, has also been tested. It was shown that serial passage induced an increasing degree of inhibitor resistance in the virus and an increasing degree of attenuation when tested in volunteers. This was observed with both an Asian strain and a Hong Kong strain. The Hong Kong virus was also passed serially at 25 degrees C in eggs but did not seem much further attenuated as a result; however, a virus strain supplied by H. F. Maassab with a much higher degree of adaptation to low temperature is being tested.Partly or completely attenuated strains have been used to induce or detect protection. Influenza B strains gave partial protection after 1 dose and almost complete protection after 2 doses and protection persisted for 7 months. A comparative study showed that there was protection after vaccination with killed virus by the parenteral route, and with live virus by the nasal route.

Genetic Variation↗
PubMed1969

Laboratory characteristics of attenuated influenza viruses.

The selection of attenuated mutants of a virus related to A2/Tokyo/3/67 and of the subtype A2/Hong Kong/1/68 is described. By passing the former in the presence of heated horse serum it was possible to obtain a strain wholly resistant to thermostable horse-serum inhibitor. A2/Hong Kong/1/68 was, however, rendered only partially resistant by this technique. In subsequent volunteer trials it was clear that inhibitor-resistance was a marker of attenuation. Residual inhibitor-sensitivity was associated with some remaining pathogenicity. Inhibitor-resistant viruses were infective and antigenic.Inhibitor-sensitive viruses were also attenuated by repeated passage at 25 degrees C. When this was attempted with the partially inhibitor-resistant form of A2/Hong Kong/1/68, the virus became over-attenuated.In the laboratory, inhibitor-resistant viruses were shown to elute more rapidly from red blood cells than their inhibitor-sensitive parents and to grow better at 40 degrees C.

Animals↗
PubMed1968

Investigetion into the attenuation of influenza viruses by serial passage.

For vaccination live viruses are better than dead ones, but live influenza vaccines are difficult to prepare. One influenza A(2) and two influenza B viruses were passed in series in embryonated eggs. At several stages of their passage they were inoculated into volunteers, and their effects assessed by virus isolations, antibody rises, and clinical reactions. The A(2) virus and one of the influenza B viruses, both of which had grown readily in embryonated eggs on first isolation, continued to induce human infections and clinical reactions after 30 egg passes. The other influenza B virus acquired enhanced human pathogenicity after three passages from man to man. After adaptation to eggs in which it at first grew reluctantly, its human virulence was appreciably reduced. It underwent no further change during a total of 20 egg passes. There was little convincing evidence of an increased incidence of clinical reactions during the winter seasons, but the numbers of volunteers were too small to draw definite conclusions.

Animals↗
PubMedDate not supplied

Experiments in the preparation of live influenza B vaccines.

A study is described of the selection of influenza B virus recombinants. Three virulent viruses isolated in 1970, 1970 and 1973, were crossed with host-range mutants of low virulence for man, which had originally been isolated in 1940, 1959 and 1956, respectively. Nine presumptive recombinants were inoculated into volunteers with low initial HI antibody titres. Although a number proved attenuated and there was evidence of high frequency of recombination, antigenic characterization of neuraminidases proved difficult. There was always some crossing between parental surface antigens, and appropriate antigenic hybrids for preparation of reference antisera were not available. Comparative virus titres at 33 degrees C and 38 degrees C were of limited value as a genetic marker. It is suggested that biological methods are unsatisfactory for the study of influenza B virus recombinants, and should be replaced by biochemical techniques designed to trace the parental origins of individual RNA segments.

Antigens, Viral↗