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Biomedical subjects

A S Beare

Publications and source records attributed to A S Beare.

18 recordsLinked to original sources
PubMed1991

Replication of avian influenza viruses in humans.

Volunteers inoculated with avian influenza viruses belonging to subtypes currently circulating in humans (H1N1 and H3N2) were largely refractory to infection. However 11 out of 40 volunteers inoculated with the avian subtypes, H4N8, H6N1, and H10N7, shed virus and had mild clinical symptoms: they did not produce a detectable antibody response. This was presumably because virus multiplication was limited and insufficient to stimulate a detectable primary immune response. Avian influenza viruses comprise hemagglutinin (HA) subtypes 1-14 and it is possible that HA genes not so far seen in humans could enter the human influenza virus gene pool through reassortment between avian and circulating human viruses.

Adult↗
PubMed1978

Trials of live influenza A recombinants in man during natural antigenic change in 1971-1976.

A long-term study is described of human trials with live recombinants derived from A/PR/8/34 (H0 N1) and successive virulent H3 N2 viruses. A/PR/8/34 was noninfectious for man and the H3 N2 strains all induced similar influenza-like illness. In each recombinant experiment, some of the progeny were adequately attenuated and potentially immunogenic. In addition, there appeared to be evidence of probable cross-protection against viruses with related but non-identical haemagglutinins. However, the degree of cross-protection depended upon the time interval between the appearance of the epidemic and vaccine viruses. Recombinants of A/PR/8/34 and a human Hsw1 strain of low virulence did not function satisfactorily, and it seemed that the suitability of A/PR/8/34 as a 'master' parent depended upon the presence of standard genetic properties in the wild parents. The replacement of A/PR/8/34 with the partially virulent virus, X-31 (H3 N2), produced a live vaccine which was infectious but poorly antigenic. A universal master strain for live influenza vaccine recombinants is probably not yet a practical possibility.

Adolescent↗
PubMed1978

Formation of antibody to matrix protein in experimental human influenza A virus infections.

Antibodies to type A influenza virus matrix protein (M) were assayed by single radial diffusion in 180 paired sera of volunteers challenged intranasally with live H3N2 viruses of varying degrees of virulence. Of these volunteers 20 had had severe clinical reactions (influenza-like); there had been 19 moderate reactions (lesser degrees of constitutional illness), and the remaining 141 reactions had been graded mild, very mild, or nil. Only 2 volunteers were shown to have antibodies to M in the pre-trial serum samples, and 11 developed anti-M rises after virus inoculation. Nine of the 11 had had severe reactions, and 2 had had moderate reactions. There was, therefore, a clear correlation between severity of clinical illness and anti-M antibody formation. In general, anti-M increases coincided with increases to the hemagglutinins and nucleoprotein, and with virus shedding. However, no anti-M antibody could be demonstrated in paired sera of 18 additional volunteers of whom 12 had developed severe reactions after the inoculation of virulent H0N1 and H1N1 influenza A viruses and of whom 12 had shown laboratory evidence of infection.

Antibodies, Viral↗
PubMed1977

RNAs of influenza virus recombinants derived from parents of known virulence for man.

Extensive use of recombinants made from A/PR/8/34 (H0N1) and wild, virulent H3N2 viruses as live influenza vaccines has provided a number of viruses of defined virulence for man. Clinical symptoms produced by these strains have ranged from febrile influenza to local coryzal symptoms or nil. A study was therefore made of the extent to which the PR8 genome had been incorporated into that of a number of the recombinants. By RNA--RNA hybridization it seemed that recombinants which had 55 per cent of greater homology with the PR8 parent were likely to conform an acceptable standard of attenuation. Those with lesser homology were frequently, but not always, clinically virulent. The technique seemed potentially useful, therefore, for screening PR8 live vaccine recombinants in vitro before giving them to volunteers.

Adolescent↗
PubMed1977

Influenza A neuraminidase antibodies in children and young adults studied by serum absorption.

A study is described of influenza A anti-neuraminidase antibodies in the sera of young people of three different groups. Each serum was individually absorbed with viruses containing the N2 neuraminidases of 1957, 1968 and 1972. Rabbit antisera prepared against the viruses were similarly absorbed. Results obtained with the animal sera suggested that these neuraminidases were antigenically distinct, but the human sera had a broader range of anti-neuraminidase activity and gave indication of asymmetric antigenic relationships. Earlier workers who surveyed anti-haemagglutinin antibodies reported that the virus of primary infection absorbed all antibodies, and the virus of secondary infection only those directed against itself. We too found that the virus of secondary infection absorbed only homologous anti-neuraminidase antibody. However, although the primary infecting virus did absorb some secondary antibody, this absorption was incomplete and it lessened with the lengthening of the time interval between the primary and secondary infecting viruses. A similar pattern was seen with anti-haemagglutinin antibodies. Absorption of anti-neuraminidase antibodies from human sera proved much more difficult than absorption of anti-haemagglutinin antibodies particularly after repeated influenza virus infections. The relative rarity of antigenic shift in the neuraminidase subunit also creates problems in the interpretation of results of serum neuraminidase antibody surveys.

Adult↗
PubMed1977

Selection of influenza B virus recombinants and their testing in humans for attenuation and immunogenicity.

The selection of influenza B virus recombinants from plaques in bovine kidney cell monolayers is described. Two sets of recombinants were each derived from parents of high and low virulence for humans, respectively. Recombination frequency was apparently high, and reassortment of genes made it possible to obtain attenuated recombinants containing the surface antigens of the virulent parents. Attenuation and immunogenicity were demonstrated in a series of volunteer trials. However, technique proved less satisfactory than for influenza A viruses which periodically undergo antigenic shift and for which there is a wide choice of parent viruses with distinctive surface antigens. In our two influenza B recombinant series there was appreciable antigenic overlap in the neuraminidases of the parents, even though in both cases these were chronologically widely separated. Another marker used was comparative titer at 35 and 38 degrees C. In practice, technical problems might sometimes make it difficult to ensure rapid production of live influenza B vaccines by recombination.

Antibody Formation↗
PubMed1976

Virulence for man of a human influenza-A virus antigenically similar to "classical" swine viruses.

The newly isolated human influenza-A strain containing swine antigens isolated in New Jersey, U.S.A., was inoculated into six volunteers. Clinical reactions were mild although all volunteers were infected. The longest period for which the virus was excreted was 8 days and the shortest 3 days. In its virulence for man the New Jersey strain was intermediate between a human and animal virus, and was quite clearly more virulent than known swine viruses. It seems possible that the outbreak in the U.S.A. was an isolated event and that the virus will not become established in man.

Antibodies, Viral↗
PubMed1976

Measurement of antibody to influenza virus neuraminidase by single radial hemolysis in agarose gels.

A simple method of assaying anti-influenza neuraminidase antibodies in human sera was described. Suitable antigenic hybrid viruses were adsorbed to sheep erythrocytes, which were then incorporated into agarose gels. When sera were introduced into wells cut in the gels, zones of hemolysis were observed in the neighborhood of those containing neuraminidase antibodies. There was a direct relationship between zone size and antibody titer. No purification of adsorbed viruses was necessary. The test was rapid, required very simple reagents, gave results that agreed well with those given by conventional techniques, and appeared to be the most sensitive of four methods evaluated. Studies of cross-reactions by hyperimmune sera against homologous and heterologous neuraminidases and of absorption of neuraminidase antibodies from human sera indicated a high degree of specificity. The technique seems to be suitable for large-scale epidemiological investigations.

Antibodies, Viral↗
PubMed1975

Trials in man with live recombinants made from A/PR/8/34 (H0 N1) and wild H3 N2 influenza viruses.

A long-term study is described of recombinant influenza viruses produced from the avirulent laboratory strain, A/PR/8/34 (H0 N1), and newly isolated H3 N2 influenza virus variants. A number of H3 H2 recombinants were found to be attenuated for man and capable of inducing antibody formation, and were therefore potentially usable as live vaccines. However, the volunteer trials as a whole suggested that, in this system, there might not be complete segregation of virulence and antigenic characteristics. No H3 N2 recombinants were detected which were non-infective for man, like the A/PR8 (H0 N1) parent, and reciprocal hybrids (H3 N1 and H0 N2) always reflected some of the virulence of the parent from which they had inherited their haemagglutinin. This property is not a feature of mouse influenza.

Animals↗
PubMed1975

A single radial haemolysis technique for the measurement of influenza antibody.

A single radial haemolysis in geltechnique has been developed for the detection and measurement of antibody to influenza haemagglutinin. The methold combines the sensitivity of haemagglutination-inhibition with the accuracy of single radial diffusion. It is simple, quick, reproducible, does not require purified or concentrated virus, and is unaffected by non-specific inhibitors. The method is particularly suitable for the routine screening of large numbers of serum samples, and may have application also to viruses other than the influenza group.

Animals↗
PubMed1975

Myxoviruses.

Myxoviruses can be divided into 2 groups, orthomyxoviruses and paramyxoviruses. the former comprise the influenza group which is subdivided into types A,B and C. Influenza B and C are purely human pathogens but influenza A, which includes a large number of antigenic subtypes, occurs in nature in pigs, horses, birds and man. All influenza A viruses irrespective of origin are chemically, biologically and genetically related. The epidemics which they cause are curious and puzzling and are an important cause of morbidity. Paramyxoviruses consist of human and animal parainfluenza viruses. The former comprise parainfluenza types 1,2,3 and 4 and mumps viruses, and, rather less certainly, measles and respiratory syncytial virus. The main animal paramyxoviruses are parainfluenza 3 (agent of shipping fever) in cattle; NDV (cause of fowl pest) and Yucaipavirus in birds; Sendai and PVM in mice; Nariva virus in rodents; possibly bovinerespiratory syncytial virus; and SV5 and SV41 in monkeys. The viruses and their place in nature will be reviewed.

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↗