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Biomedical subjects

R G Webster

Publications and source records attributed to R G Webster.

At least 397 records · Page 22Linked to original sources

Strains of Hong Kong influenza virus in calves.

Three strains of Hong Kong influenza virus isolated from humans were compared with a strain isolated from a calf for their ability to cause disease in calves. One of the human strains. A/Aichi/2/68, was detected for five days in a calf, but all three failed to cause signs of disease. Strain A/cal/Duschanbe/55/71 could be detected for seven days and caused an influenza-like illness in calves.

Animals↗

Reactogenicity and immunogenicity of bivalent influenza A and monovalent influenza B virus vaccines in high-risk children.

Seventy-nine high-risk children were immunized with either commercial, bivalent, split-product influenza A vaccine or purified hemagglutinin-neuraminidase bivalent influenza A vaccine, and 78 of these subjects were immunized with commercial, monovalent, influenza B split-product vaccine. The reactogenicity of all three vaccines was low, and there were no severe reactions. Twenty-nine subjects who received hemagglutinin-neuraminidase vaccine as their initial dose and commercial split-product vaccine as a booster dose had significantly lower antibody responses to influenza A/New Jersey/76 virus than subjects who received two doses of commercial split-product vaccine. The responses of the two groups to influenza A/Victoria/75 virus were comparable. Twenty-four subjects with malignancy who were receiving chemotherapy were compared with a group of subjects matched for age and vaccine preparation. Patients with cancer had significantly lower antibody responses to A/New Jersey/76 virus than patients without cancer. The ultimate responses of patients with cancer to A/Victoria/75 and B/Hong Kong/72 viruses were comparable to those of other patients, but early responses were lower.

Adolescent↗

Matrix protein from influenza A virus and its role in cross-protection in mice.

The matrix (M) protein of influenza A virus, one of the two group-specific internal proteins of the virion, was isolated in a pure form, and its immunogenicity was stable to heating at 100 degrees C for 2 min. Mice immunized with isolated M protein in complete Freund adjuvant and subsequently infected with influenza virus cleared virus more rapidly from their lungs than did unimmunized mice. Despite the rapid clearance of virus, the mice developed pneumonia that was at least as severe as in unimmunized mice. Preliminary studies suggest that the rapid clearance of influenza virus from the lungs of mice immunized with M protein may be initiated by a cell-mediated rather than a humoral response. The mechanism by which a cross-reactive internal virion protein can initiate clearance of the different subtypes of influenza is not clear. Perhaps the M protein is exposed on the surface of the virus-infected cell and is responsible for the cross-reactivity at the cytotoxic T-cell level recently detected between influenza A virus subtypes.

Animals↗

Isolation and characterization of influenza A viruses from avian species in Hong Kong.

Surveillance of apparently healthy ducks, chickens, and geese at a poultry dressing plant in Hong Kong yielded 51 haemagglutinating viruses 25 of which were influenza A viruses. Of these, 24 were subtyped into 13 combinations based on haemagglutinin and neuraminidase surface antigens. Of the 13 different influenza A viruses isolated, 7 possessed combinations of haemagglutinin and neuraminidase subunits that have not been reported previously-i.e., Hav2N1, Hav2Nav5, Hav4N2, Hav7N2, Hav7Nav1, Hav7Nav3, and Hav7Nav6. Four of the isolates were non-avid: they were not neutralized by antisera to any of the reference subtypes of influenza A viruses, yet antisera to each isolate inhibited both that virus and a known reference strain. The large number of combinations of haemagglutinin and neuraminidase and the isolation of two different influenza A viruses from one duck suggests that recombination may be occurring in nature.

Animals↗

Potentiation of the immune response to influenza virus subunit vaccines.

Influenza subunit vaccines are poorly immunogenic in unprimed lower animals and man and methods were sought to potentiate the humoral response. Influenza B intact virus vaccines potentiated the antibody response of hamsters to purified vaccines containing influenza A hemagglutinin and neuraminidase subunits. The levels of anitbody induced were at least as high as those induced by equivalent doses of whole virus. Similarly, intact heterologous influenza A virus vaccine (A/Victoria/3/75 [H3N2]) potentiated the antibody response of hamsters to A/NJ/76 [Hswl NI] subunit vaccines but large doses of intact virus were required. Considerably lower doses of homologous intact A/NJ/76 [Hswl NI] potentiated the antibody response of hamsters and sero-negative people to subunit vaccines. This suggests that future influenza subunit vaccines for use in seronegative people should contain a minimal dose of whole virus vaccine sufficient to potentiate the immune response to the subunits but insufficient to be reactogenic. A synthetic water soluble adjuvant (N-acetyl-muramyl-L-alanyl-D-isoglutamine) was also shown to potentiate the immune response of hamsters to A/NJ/76 [Hswl NI] influenza virus subunit vaccines.

Adjuvants, Immunologic↗

Influenza virus subunit vaccines. II. Immunogenicity and original antigenic sin in humans.

Subunit vaccines containing hemagglutinin, neuraminidase, and nucleocapsids of A/Port Chalmers/1/73 (H3N2) influenza virus were prepared after treatment of purified virus with ammonium deoxycholate. The immunogenicity of these subunits and the response to the common and specific antigenic determinants on the hemagglutinin subunits were studied in man. The subunits were as immunogenic in man as intact inactivated influenza virus vaccine at an equivalent concentration. Booster doses of antigen did not increase the antibody responses. Intact influenza B virus vaccine did not potentiate the immune response to the type A subunits in man. Volunteers responded differently to the common and specific determinants on the hemagglutinin subunits. The predominant antibody response was to the common or cross-reacting determinants present on hemagglutinins of both A/Hong Kong/1/68 (H3N2) and Port Chalmers/73 virus. Some men who failed to produce specific antibodies to the hemagglutinin of Port Chalmers/73 virus responded to the specific determinants on the Hong Kong/68 hemagglutinin. Higher doses of the subunit vaccines (1,400 chick cell-agglutinating units) did induce antibodies to the specific determinants on the Port Chalmers/73 virus hemagglutinin as well as to the common and specific determinants on Hong Kong/68 influenza virus.

Animals↗

Ortho- and paramyxoviruses from migrating feral ducks: characterization of a new group of influenza A viruses.

Ortho- and parainfluenza viruses isolated from the cloacas of migrating feral ducks shot on the Mississippi flyway included three strains of influenza. A virus (Hav6 Nav1, Hav6 Nl, Hav7 Neq2) as well as Newcastle disease virus. One influenza virus, A/duck/Memphis/546/74, possessed Hav3 haemagglutinin, but the neuraminidase was not inhibited by any of the known influenza reference antisera. The neuraminidase on this virus was related to the neuraminidases on A/duck/GDR/72 (H2 N?), A/turkey/Ontario/7732/66 (Hav 5 N?), A/duck/Ukraine/1/60 (Hav3 N?) and A/turkey/Wisconsin/68. We therefore propose that the neuraminidase on this group of influenza viruses be designated Nav6. The A/duck/Memphis/546/74 influenza virus caused an ocular discharge in 1 of 5 ducks and was shed in faeces for 10 days; it was stable in faecal samples for up to 3 days at 20 degrees C. These results suggest that ecological studies on influenza in avian species should include attempts to isolate virus from faeces. Faecal-oral transmission is an attractive explanation for the spread of influenza virus from feral birds to other animals.

Animals↗

Immunotherapy of osteosarcoma patients with virus-modified tumor cells.

Twelve patients 11-20 years of age with recurrent osteosarcoma were immunized with either autologous or allogeneic tumor cells infected with influenza virus, strain B/Michigan or A/Port Chalmers. Six patients received only the vaccine, and the remaining six patients continued to receive methotrexate chemotherapy. The main objectives of this study were to determine if immunizations were toxic, if antibodies developed to the influenza virus antigen component of the vaccine, if this vaccine increased tumor-specific cellular and humoral immunity, and if the increase in immune response could be correlated with clinical course and prognosis. In all 12 cases, toxicity was negligible, and immunizations boosted antibody titers to both tumor cell and influenza virus antigens. However, in four of the six patients with advanced disease who received immunotherapy only, the vaccine did not stimulate mixed lymphocytes nor did it increase cell-mediated immunity. By contrast, five of six patients with minimal disease who continued methotrexate therapy developed cellular and humoral immunity in response to both allogeneic and autologous tumor cells. Although no clear-cut relationship between responses to the tumor cell vaccine and clinical course and prognosis could be demonstrated, three of the six patients with minimal disease have survived for 7-8 months after the first vaccination, without progression of disease. This study demonstrates that plasma membrane preparations derived from different lines of virus-infected osteosarcoma tumor cells will elicit an antibody response in patients with drug-resistant progressive osteogenic sarcoma.

Adolescent↗

Characterization of avian influenza viruses. Designation of a newly recognized haemagglutinin.

Studies with specific antisera to the haemagglutinin and neuraminidase antigens of all the influenza A subtypes show that A/turkey/Wisconsin/66 influenza virus, originally included in the Hav6 subtype, does not react in either haemagglutinin inhibition or immunodiffusion tests with antisera to Hav6. It is therefore proposed that A/turkey/Wisconsin/66 be placed in a new subtype designated Hav9. The neuraminidase antigens of the Hav6 subtype were further characterized and were shown to be N1, N2, Neq2, and Nav5 subtypes. Hav6 influenza viruses isolated from turkeys over an 11-year period showed little antigenic drift. The haemagglutinin and neuraminidase of A/shearwater/Australia/72 (Hav6Nav5) were identical with those of a virus isolated 8 years previously from a turkey in California: A/turkey/California/64 (Hav6Nav5).

Agglutinins↗

Diversity of the antibody response to the different antigenic determinants on the hemagglutinin subunits of influenza viruses.

Sera from rabbits hyperimmunized with hemagglutinin (HA) subunits isolated from the A/Port Chalmers/73 (H3N2)strain of influenza virus showed great differences in their cross-reactions with different strains of influenza virus. In hemagglutination-inhibition tests, some sera reacted to about the same titer with A/Port Chalmers/73 and A/Hong Kong/68 viruses, suggesting that these two strains were very closely related. Other sera, which reacted to high titer with A/Port Chalmers/73 virus, had only a low titer with the Hong Kong/68 strain, suggesting that the two viruses were distantly related. Evidence suggested that these diverse cross-reactions were due to widely different ratios, in the different sera, of antibodies to the "common" and the "specific" antigenic determinants on the HA subunits. Thus, some rabbits gave a stronger response to the "common" determinants than to the "specific", whereas in others, the reverse seemed to be the case. Sera from human volunteers injected with A/Port Chalmers/73 inactivated or subunit influenza virus vaccines, or from people infected with Port Chalmers/73 virus, contained, in most cases, antibodies predominantly to the "common" antigenic determinants on the HA subunits. These sera reacted to higher titer with Hong Kong/68 virus than with the Port Chalmers/73 strain. Absorption of these sera with Hong Kong/68 virus totally removed all detectable antibody, suggesting that they contained no antibody to the "specific" determinants of Port Chalmers/73 HA. Paradoxically, absorption of the sera with Port Chalmers virus did not remove all antibodies, suggesting that the sera contained antibodies to the "specific" determinants on Hong Kong/68 HA.

Absorption↗

Orthomyxoviridae.

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Orthomyxoviridae↗