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Biomedical subjects

R Jennings

Publications and source records attributed to R Jennings.

At least 109 records · Page 6Linked to original sources

The effect of bacterial peptidoglycans on the immune response of hamsters to influenza virus vaccines.

The immune response of hamsters to influenza virus vaccine incorporating peptidoglycans derived from Streptomyces griseus was investigated. The results showed that although inoculation of a subunit influenza virus vaccine together with a peptidoglycan elicited a markedly increased serum HI antibody response compared to that induced by the subunit vaccine alone, pre-treatment of animals with peptidoglycans resulted in a suppression of the antibody response to the vaccine haemagglutinin antigen. The immunosuppressive effect was dose-related, and could be shown by adoptive transfer experiments to be transferred by spleen cell preparations from peptidoglycan-treated hamsters. The reasons for these findings, and their implication for the use of peptidoglycans as 'carriers' in influenza virus subunit vaccines, are discussed.

Animals↗

The spread and persistence of influenza viruses in normal and cyclophosphamide-treated mice.

The persistence and extrapulmonary spread of three strains of influenza virus, the mouse neuro-adapted A/NWS virus, the wild-type strain A/Victoria/75, and a recombinant virus RIT4050, bearing surface antigens derived from A/Victoria/75, were studied in both normal and cyclophosphamide-treated CBA mice following either intranasal or intracerebral inoculation. All three viruses showed increased lethality in mice in the presence of cyclophosphamide but exhibited distinctive patterns of replication and spread. The recombinant virus RIT4050 showed a reduced ability to replicate, persist, and spread in CBA mice compared to either A/NWS or A/Victoria/75 viruses, and in general, the A/NWS virus persisted to a greater extent than the A/Victoria/75 virus in both normal and treated mice. However, in the presence of cyclophosphamide, no extrapulmonary spread of A/NWS virus was observed. The reasons for the differences are discussed.

Administration, Intranasal↗

Use of the enzyme-linked immunosorbent assay (ELISA) for the estimation of serum antibodies in an influenza virus vaccine study.

The value of the enzyme-linked immunosorbent assay (ELISA) for determining the serum antibody responses of volunteers following immunisation with various inactivated influenza virus vaccines was assessed, and the incidence of seroconversions, as measured by both haemagglutination-inhibition (HI) and ELISA response of the volunteers determined. ELISA was found to be more sensitive than the HI test in detecting serum antibodies, but was also less specific under the conditions used. With regard to efficacy, the whole virus vaccine proved to be more effective in inducing serum antibody in an unprimed population than either tween-ether split or subunit adsorbed vaccines, but the reverse situation held when the population was primed with respect to the antigen concerned.

Adolescent↗

The amantadine-sensitivity of recombinant and parental influenza virus strains.

Several wild-type influenza A strains together with recombinants derived from these strains, were tested for sensitivity to amantadine using the in vitro techniques of inhibition in egg-bit culture and plaque reduction in MDCK cells. The results obtained were analysed with reference to the derivation of the recombinants. Susceptibility to amantadine was related to the gene coding for matrix protein, and these data are in agreement with previous reports of studies using other series of influenza viruses.

Amantadine↗

Responses of volunteers to inactivated influenza virus vaccines.

Three different types of bivalent influenza virus vaccine, a whole virus, an aqueous-surface-antigen vaccine and an adsorbed-surface-antigen vaccine were tested at three dosage levels in volunteers primed with respect to only one of the haemagglutinin antigens present in the vaccines. The local and systemic reactions to all three vaccine types were mild in nature and, following first immunization, the aqueous-surface-antigen vaccine was the least reactogenic. The serum haemagglutination-inhibiting antibody response to the A/Victoria/75 component of the vaccines to which the volunteer population was primed, was greatest following immunization with the aqueous-surface-antigen vaccine; the greatest antibody response to the A/New Jersey/76 component of the vaccines was observed following immunization with whole virus vaccine.

Adolescent↗

Antigenicity in hamsters of inactivated vaccines prepared from recombinant influenza viruses.

Inactivated vaccines prepared form influenza virus strains obtained by the recombination of A/PR/8/34 (H1N1) or A/FM/1/47 (H1N1) viruses with A/Victoria/3/75 (H3N2) virus, were tested for their antigenicity in hamsters. The parental origin of the genes of each cloned recombinant virus was determined by polyacrylamide gel electrophoresis, and vaccines prepared from each strain by concentration, purification on sucrose density gradients and inactivation with formalin. All the recombinant strains used in these studies possessed surface haemagglutinin and neuraminidase antigens derived from the A/Victoria/75 parent strain. On inoculation into hamsters, at equivalent concentrations, these vaccines varied in their ability to induce haemagglutination-inhibiting (HI) antibodies in the serum. This variation was not dependent on concentration and was observed using neutralization and single radial haemolysis, as well as HI. The possible reasons for the findings are discussed.

Animals↗

Growth of influenza A viruses in hamsters.

The growth characteristics of four temperature-sensitive or cold-adapted recombinant influenza viruses and eight recombinant influenza viruses derived in other ways, together with the wild-type, parent viruses of these strains, were tested in hamster lungs and turbinates and in embryonated eggs at different temperatures for their replicative ability. The results showed that although the temperature-sensitive and cold-adapted recombinant viruses replicated to considerably lower titres than their wild-type parent virus strains in hamster lung and at 37 degrees C in embryonated eggs, no similar pattern of growth was observed for the group of A/PR 8 and A/Okuda recombinant influenza viruses studied in these systems. The hamster model is not therefore generally applicable as a marker for attenuated influenza virus vaccine strains.

Animals↗

The replication of type A influenza viruses in the infant rat: a marker for virus attenuation.

Twenty recombinant influenza virus strains bearing HSw1N1, H1N1 or H3N2 surface antigens, together with their respective wild-type or laboratory-propagated parent viruses, were inoculated into 2 day-old infant rats and their replication in the turbinates and lungs of these animals observed over a period of 5 days. In addition, the ability of each of the recombinant and parent viruses to enhance a subsequent infection of these infant rats by Haemophilus influenzae type b was determined. The results showed that both parent and recombinant viruses replicated less well in the lungs than in the turbinates of infant rats, but the titres in both tissues were generally lower for the recombinant strains. The capacity of the majority of the recombinant influenza viruses to promote bacterial infection of the infant rats, as determined by the incidence of H. influenzae bacteraemia and meningitis, was also markedly less than that of their parent viruses. A correlation between virulence for man and both the replication in infant rat turbinates and the ability to enhance H. influenzae infection, was established for the virus strains studied. The data are discussed in relationship to the value of the infant r-H influenzae system as a laboratory marker for the determination of the virulence of influenza virus strains.

Animals↗

Influenza virus infection of newborn rats: virulence of recombinant strains prepared from influenza virus strain A/Okuda/57.

Infant rats were infected intranasally with wild influenza virus strains, attenuated strain A/Okuda/57 or recombinants prepared from these parents. The growth of viruses in the turbinates or lungs, and the ability of virus infections to potentiate subsequent bacterial infection by Haemophilus influenzae (HIb) were measured. The two wild strains of virus and a recombinant strain WRL105, known to be virulent for man, reached titres of 10(5.1)--10(6.5) EBID50/ml in the turbinates of infant rats 48 h after infections; infection by these viruses was followed by HIb bacteraemia in 77--92% and meningitis in 58--75% of animals. In contrast, virus strains known to be attenuated for man grew to lower titres in infant-rat turbinates and promoted a lower incidence of systemic infection by HIb than the virulent strains. A comparison of the various results of infection of infant rats with influenza virus strains of known pathogenicity for man indicated that the subsequent incidence of HIb bacteraemia was the most discriminating measurement of virus virulence; the range of yields of attenuated virus in rat turbinates overlapped that of virulent strains. These results, together with those of previous studies, indicate that the behaviour of influenza viruses in infant rats is an indication of virus virulence for man, and could provide a test of virulence that would facilitate the development of live attenuated virus vaccines for human use.

Animals↗

Influenza virus infection of the guinea pig: immune response and resistance.

Guinea pigs were inoculated by intranasal inoculation with unadapted, influenza virus A/England/42/72, and virus was recovered from nasal washings between 3 and 10 days post-inoculation. Infected animals did not exhibit a febrile response to infection, did not produce local antibody and produced only relatively low levels of serum antibody. However, they developed delayed-type hypersensitivity to influenza virus, demonstrable by both skin tests and macrophage migration inhibition tests, which was similar to that of man. The relevance of the influenza virus specific delayed hypersensitivity in immunity to infection was examined in this model. Guinea pigs previously infected with virus or passively immunized with hyperimmune serum were relatively resistant to reinfection with influenza virus A/England/42/72. Inoculation of guinea pigs with spleen cells from immune donor animals, together with or without immune serum, did not give or enhance resistance to challenge virus infection. The results do not suggest a role for delayed hypersensitivity response in immunity to influenza virus infection.

Animals↗

Influenza virus infection of a newborn rats: virulence of recombinant strains prepared from a cold-adapted, attenuated parent.

Infant rats were infected with one of a series of influenza A viruses. The growth of viruses in the turbinates or lungs, and the ability of virus infection to potentiate a subsequent bacterial infection by Haemophilus influenzae (HIb), were measured. The three virus strains known to be virulent for man grew to relatively high titres of 10(5.2)--10(6.8) EBID50/ml in the turbinates of infant rats at 48 hours post-infection, and virus infection enhanced subsequent systemic infection following intranasal inoculation of rats with HIb. In contrast, influenza virus A/Ann Arobr/6/60--P17 and the three recombinant viruses prepared from this strain, all of which are attenuated for man, replicated to significantly lower titres of 10(2.6)--10(4.1) EBID50/ml in infant rats turbinates, and failed to promote systemic infection by HIb to the samest that the behaviour of influenza viruses in infant rats may be an indication for virus virulence for man, and thus provide a test which could facilitate the development of live, attenuated virus vaccines.

Animals↗

The specificity of the anti-haemagglutinin antibody response induced in man by inactivated influenza vaccines and by natural infection.

The anti-haemagglutinin antibody response in adult human volunteers to inactivated whole virus or tween ether split influenza A/Victoria/75 (H3N2) and A/Scotland/74 (H3N2) virus vaccines was investigated using antibody absorption and single-radial-haemolysis (SRH) techniques. The concentrations of haemagglutinin (HA), nucleoprotein (NP) and matrix (M) antigens measured by single radial diffusion (SRD) and rocket immunoelectrophoresis were similar for both the whole virus and split vaccines. Whole virus and split vaccines induced crossreactive (CR) antibody in 87% of vaccinees. Strain specific (SS) antibody to A/Hong Kong/1/68 of the homologous virus was induced less frequently than CR antibody. Higher anti-haemagglutinin antibody titres were detected in persons receiving the split virus vaccines than in those receiving the whole virus vaccines. No antibody to the type-specific matrix protein was detectable, but 33% of volunteers developed an antibody rise to type-specific nucleoprotein antigen. The specificity of the anti-haemagglutinin antibody response in human adults to natural infection with A/Port Chalmers/73 (H3N2) virus was similar to that induced by inactivated vaccines in that a high proportion of subjects developed CR anti-haemagglutinin antibody, which reacted with A/Hong Kong/68 virus and the homologous A/Port Chalmers/73 virus, and SS antibody for A/Hong Kong/68 virus but SS antibody for A/Port Chalmers/73 virus was infrequently stimulated by natural infection.

Adult↗

The infant rat as a model for assessment of the attenuation of human influenza viruses.

The intranasal infection of infant rats with Haemophilus influenzae type b can be considerably enhanced by prior infection of the rats with influenza virus. When influenza virus A/England/939/69 was used to infect the animals a minimum of 10(4-0) EID50 was required to enhance H. influenzae infection; infection with 4 x 10(6) H. influenzae bacteria was needed to reveal this enhancement and infant rats two days old at the time of virus inoculation had to be used. By this method, nine strains of influenza virus were assessed for their ability to enhance H. influenzae infection, and the results were compared with their known virulence for man. The results showed a close correlation in this respect for all of the viruses, except strain A/PR/8/34. The replication of these viruses in infant-rat turbinates and lungs was also studied; virus concentrations in turbinate tissues 48 h after infection showed a close correlation with virulence for man. Thus, three influenza virus strains known to be virulent for man reached concentrations in infant-rat turbinates ranging from 10(4-8) to 10(5-7) EBID50/0-05 ml at 48 h; the concentrations of six viruses known to be attenuated or non-infectious for man grew less well in infant rat turbinates, and reached concentrations at 48 h of 10(1-0) to 10(3-5) EBID50/0-05 ml. The results are discussed in relation to the use of the infant-rat model for assessment of the attenuation of candidate live influenza virus vaccine strains.

Animal Population Groups↗

Reactogenicity and immunogenicity of a surface-antigen-adsorbed influenza virus vaccine in children.

An influenza virus vaccine containing the purified surface haemagglutinin and neuraminidase antigens of A/Victoria/75 and B/Hong Kong/73 viruses adsorbed to an aluminium hydroxide gel was assessed for reactogenicity and immunogenicity in children aged 4 to 11 years, since there is no influenza virus vaccine available for this age group. Significant serum haemagglutination-inhibiting antibody responses to the A/Victoria/75 and B/Hong Kong/73 haemagglutinin antigens present in the vaccine were observed in 47% and 35%, respectively, of the children vaccinated, with a single dose. The vaccine induced no significant local or systemic reactions.

Antibodies, Viral↗