Search PubMed⌕ Search

Biomedical subjects

R Jennings

Publications and source records attributed to R Jennings.

At least 127 records · Page 7Linked to original sources

A contribution of cellular immunity to protection against influenza in man.

The degree of lymphocyte transformations and leukocyte migration inhibition (LMI) in the presence of inactivated A/Scotland/74 (H3N2) influenza virus vaccine was measured in blood samples collected from 56 medical student volunteers. At the same time the volunteers were skin tested, using the same vaccine. Using the antigenically similar WRL 105 (H3N2), recombinant influenza virus, the level of haemagglutination-inhibiting (HI) antibodies in serum, and neutralizing antibodies in nasal washings collected from the volunteers, were also determined. Each volunteer was then inoculated with live, attenuated WRL 105 influenza virus vaccine and infections demonstrated by virus isolations and serology. Correlations between the ability to infect the volunteers and the various parameters of humoral and cellular immunity were then determined. The results showed a good correlation between the level of serum HI antibody and infection. Thus 16 of 20 volunteers with serum HI antibody titres of 1:10, but only 6 of 20 volunteers with antibody levels of 1:30, showed evidence of infection. No direct correlation was observed between any of the other parameters measured and infection by WRL 105 virus. However, when the LMI and serum HI antibody levels were considered together, a contribution of cellular immunity, as measured by the LMI test, could be found. Of 19 volunteers with low serum HI antibody and low LMI levels, 16 were infected, whereas of 13 volunteers with low HI antibody, but with high LMI levels, only 6 showed evidence of infection with WRL 105 influenza virus.

Adult↗

Influenza virus infection in newborn rats: a possible marker of attenuation for man.

The growth of parent influenza viruses A/England/939/69 and A/PR/8/34, and clones 6, 7, and 64C, derived by recombination, was studied in newborn rats. Using an inoculum of 10(4.0) EID50, influenza virus A/England/939/69 produced the highest titres of virus in rat turbinates at 48 hours after inoculation; clones 6 and 7 and A/PR/8/34 grew to lower titres; and clone 64C grew to the lowest titre. These differences were less apparent when 10(2.0) EID50 of virus was used as an inoculum, and rats were not infected by smaller inoculum of any of the virus strains. Infection with 10(4.0) EID50 of all viruses produced lung infection; at 48 hours after infection, the highest titres were recovered from rats infected with A/PR/8/34 and A/England/939/69 virus. Prior infection with A/England/939/69 or A/PR/8/34 increased the incidence of bacteraemia and meningitis following intranasal inoculation of Haemophilus influenzae type b; infection with clone 64C did not enhance bacterial meningitis, while infection with clone 6 gave an intermediate result. Volunteer studies with these viruses have shown that influenza virus A/England/939/69 was virulent, clones 6 and 7 were attenuated, clone 64C was over-attenuated, and A/PR/8/34 virus was noninfective for man. The relative titres of virus recovered from turbinates taken 48 hours after infection with 10(4.0) EID50 of virus and the ability of virus infection to enhance bacterial infection correlated with the property of virus attenuation for man for four of the five strains tested; however, no correlation was seen for A/PR/8/34 virus, which is a result also found in other laboratory tests designed to measure virulence for man.

Animals↗

Reactogenicity and immunogenicity of whole and ether-Tween-split influenza A virus vaccines in volunteers.

Two separate, double-blind studies were carried out in volunteers to compare the reactogenicity of, and serum antibody responses to, whole or ether-Tween-split inactivated influenza virus vaccines. In both studies the ether-Tween-split vaccines induced a lower rate of reactions. The serum hemagglutination-inhibiting (HAI) antibody response of volunteers to the A/Scotland/74 component of the split vaccine used in the first study was significantly greater than that following inoculation of A/Scotland/74 whole-virus vaccine. The neuraminidase-inhibiting (NI) antibody responses of the volunteers to each vaccine were similar. In the second study, a markedly better NI antibody response to the influenza A virus component was seen following immunization with split-virus vaccine, but the HAI antibody response to both split and whole vaccines was the same. In both studies the serum HAI antibody responses to the B/Hong Kong/73 component of the vaccines were similar. Challenge of the volunteers with attenuated influenza viruses homologous to the influenza A component of the vaccines showed both types of vaccines to be protective.

Antibodies, Viral↗

Immunity to attenuated influenza virus WRL 105 infection induced by heterologous, inactivated influenza A virus vaccines.

Groups of student volunteers were immunized with one of five different inactivated influenza virus vaccines. The concentration of virus in the various vaccines differed by both the international unitage test and by the concentration of haemagglutinin, as measured by the single radial diffusion test; the results of the two methods of standardization showed no correlation. The serum HI response to immunization was variable; volunteers given A/England/72 showed a 16.6-fold increase in homologous serum antibody titre whilst volunteers given A/Hong Kong/68 vaccine showed a 4.2-fold increase. The variable response of volunteers to immunization could not be explained by the varied concentration of virus in the vaccines, as measured by either test, the titres of serum HI antibody present before immunization, or a combination of these two factors.The ability to infect volunteers with WRL 105 virus 4 weeks after immunization with heterologous, inactivated virus vaccine was directly related to the degree of cross-reactivity between the haemagglutinins of this vaccine virus and WRL 105 virus. Thus, the greatest number of infections by the challenge virus were seen in volunteers given A/Hong Kong/68 vaccine, less were observed in volunteers given A/England/72 vaccine, and least were found in groups given A/Port Chalmers/73 or A/Scotland/74 vaccine. However, compared with the incidence of infection in volunteers given B/Hong Kong/73 vaccine, all the heterologous influenza A vaccine gave some immunity to challenge infection.

Antibodies, Viral↗

Dose-response relationship after immunization of volunteers with a new, surface-antigen-adsorbed influenza virus vaccine.

Volunteers (15 per group) were given inoculations of various doses (5-400 international units [IU]) of surface-antigen-adsorbed influenza virus A/Port Chalmers/73 vaccine; this vaccine was prepared from purified virus hemagglutinin and neuraminidase antigens and adsorbed to alhydrogel. The titers of hemagglutination-inhibiting (HAI) and neuraminidase-inhibiting antibodies in serum after immunization showed a clear dose-response relationship. Thus, for volunteers given 400, 100, 25, or 5.0 IU of vaccine, the titers of HAI antibody in serum increased 174-, 32-, 12-, and eightfold, respectively. A similar dose response was observed for production of local neutralizing antibody. Immunization with A/Port Chalmers/73 virus vaccine also induced serum HAI antibody to influenza viruses A/Scotland/74, A/England/72, and A/Hong Kong/68; the increase in titers of antibody to these viruses corresponded directly to the degree of cross-reactivity between the virus tested and the vaccine virus. Four weeks after immunization, all volunteers were challenged with attenuated WRL-105 influenza virus. Evidence of viral infection was found in one, two, and two volunteers in each group of 15 subjects previously immunized with 400, 100, and 25 IU of vaccine, respectively; in six of the 15 volunteers given 5.0 IU of vaccine; and in 10 of 15 control subjects. The results suggest that equivalent immunity was induced in volunteers given greater than or equal to 25 IU of vaccine.

Adult↗

The hamster as an experimental animal for the study of influenza. I. The role of antibody in protection.

Hamsters were used to examine the role of serum antibody in protection against influenza virus infection. Following intranasal instillation, influenza viruses replicated well in these animals, and high, reproducible amounts of virus could be subsequently recovered from nasal washings and lung suspensions. A specific serum antibody response to the infecting virus was also observed; but no local antibody production was detected. The passive transfer of serum antibody gave some measurable protection, against homologous influenza virus challenge, to recipient hamsters. However, evidence that protection can occur in the absence of detectable serum antibody in individual hamsters, is also presented.

Animals↗

The hamster as an experimental animal for the study of influenza. II. The role of spleen cells in protection.

Hamsters previously infected by influenza viruses, have been shown to have a cell-mediated immune response, as measured by the macrophage migration inhibition test. The participation of spleen cells in the protection of recipients against homologous influenza virus infection was also demonstrated using adoptive transfer experiments. However, the protection achieved by spleen cell transfer was marginal and not observed in every animal. The time at which the spleen cells were transferred following infection, and their number, affected the outcome. Evidence suggesting that transferred spleen cells protected recipient hamsters through specific antibody is presented.

Animals↗

Immunity following intranasal administration of an inactivated, freeze-dried A/England/42/72 vaccine.

A group of 23 student volunteers were each inoculated intranasally with 400 IU of inactivated, freeze-dried A/England/42/72 vaccine. Only one volunteer showed a four-fold rise in serum HI antibody following immunization, and the mean increase in serum HI antibody (gmt) for all volunteers did not increase two-fold. Thirteen of the volunteers developed detectable levels of nasal wash neutralizing antibody after immunization; local antibody was most commonly found in volunteers who produced a detectable but less than four-fold fise in serum antibody titre, and who produced nasal washings with relatively high concentrations of protein and secretory IgA. Four weeks after immunization, the vaccinees and a matched group of control subjects were inoculated with attenuated A/England/42/72 (MRC-7) virus. Evidence of infection was found in 14 of 23 (61 per cent) of control subjects and in seven of 23 (30 per cent) of immunized volunteers. This result showed a significant protection (P = 0.04) against challenge virus infection for volunteers given intranasal vaccine.

Administration, Intranasal↗

A new, surface-antigen-adsorbed influenza virus vaccine. I. Studies on immunogenicity in hamsters.

The ability of a new, surface-antigen-adsorbed influenza virus vaccine to induce serum antibody in hamsters, and to protect these hamsters against subsequent homologous virus challenge, is reported. In addition, similar studies in hamsters have also been carried out using the surface antigen material prior to adsorption to the aluminium hydroxide carrier. The new, adsorbed vaccine is at least as effective as inactivated saline influenza virus vaccine in inducing serum antibody and protection in hamsters; the unadsorbed surface antigen material, however, did not confer protection to hamsters challenged subsequently with homologous virus.

Adsorption↗

A new surface-antigen-adsorbed influenza virus vaccine. II. Studies in a volunteer group.

A group of 23 volunteers were each inoculated with 600 CCA of a new form of influenza virus A/England/42/72 vaccine; this vaccine consisted of purified haemagglutinin and neuraminidase antigens adsorbed to alhydrogel. No significant reactions to the vaccine were reported. Twenty-two volunteers produced increased titres of serum HI antibody, and all showed increased titres of NI antibody after immunization. Thus, for volunteers with no pre-immunization serum HI antibody, the geometric mean titre of serum antibody increased from 1/5 to 1/196 after immunization. Ten volunteers developed local neutralizing antibody after immunization; this antibody response was detected most frequently in volunteers who showed the greater serum antibody response to immunization, and in nasal washings with the higher concentrations of protein and IgA. Ten weeks after immunization, the vaccinees and a group of matched controls were inoculated intranasally with attenuated A/England/42/72 virus. Evidence of infection with the challenge virus was found in 14 of the control subjects and in one of the vaccinees. The results indicate that the surface-antigen-adsorbed vaccine induced high titres of serum antibody, and gave significant protection against challenge infection.

Adsorption↗