D. Hobson

The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses

The intranasal inoculation of volunteers with living partially attenuated strains of influenza A and B viruses offers a new opportunity to determine the protective effect of serum haemagglutin-inhibiting antibody against a strictly homologous virus, under conditions where the time and dosage of the infective challenge can be controlled, the scoring of proven infections can be more precise and higher rates of infection can be achieved than in most natural epidemics.In 1032 adult volunteers, whose serum HI antibody titre was determined immediately before virus challenge, there was a consistent inverse quantitative relationship between the HI titre and the likelihood of infection. The PD 50 (50% protective dose) of HI antibody was 1/18-1/36, but an unusual finding was that volunteers with no detectable pre-challenge antibody often seem to be less susceptible to infection than those with pre-challenge antibody in low titre.In one group of volunteers challenged with an influenza B strain there was no evidence that pre-challenge antibody titres against viral neuraminidase had any significant protective effect against challenge infection.

A COMPARISON OF LIVE AND KILLED INFLUENZA-VIRUS VACCINES: Report to the Medical Research Council's Committee on Influenza and other Respiratory Virus Vaccines

Abstract 98 volunteers were vaccinated with formalin-inactivated influenza-B virus intramuscularly or with living influenza-B virus intranasally. They, and a group of control volunteers, were subsequently challenged with live virus administered intranasally. 71% of those given killed vaccine developed an antibody response but 15% were infected on challenge. 51% of those who had received live virus had an antibody response and 2% were infected on challenge. Vaccination also reduced the frequency of clinical reactions. The living vaccine used in this trial produced too many reactions to be used on a large scale.

Factors affecting the sensitivity of replicating McCoy cells in the isolation and growth of chlamydia A (TRIC agents).

Normal non-irradiated McCoy cell cultures provide a sensitive and reproducible method for the isolation of oculo-genital strains of chlamydia A directly from human secretions and for laboratory studies with these agents. Since September 1973, chlamydia have been isolated from 175 of 562 women (32-1%) attending venereal disease clinics. Freshly isolated and low passage strains have been used to determine the importance of centrifugation, constitution and pH of the tissue culture medium, and the temperature of incubation in controlling the efficiency of plating in the method.

The efficacy of live and inactivated vaccines of Hong Kong influenza virus in an industrial community. A report to the Medical Research Council Committee on influenza and other respiratory virus vaccines.

Intranasal vaccines of inactivated or living attentuated A2/Hong Kong influenza viruses were compared for clinical acceptability, serological effects and protective efficiency against natural epidemic influenza in a large industrial and clerical population.Neither vaccine resulted in any significant untoward side-effects. The serum haemagglutination-inhibiting (HI) antibody response within 1 month of vaccination was similar with both vaccines; approximately 50% of those with little or no pre-vaccination antibody developed 4-fold or greater rises in titre. The effect of the antigenic potency of the vaccines and the prior immunological experience of the population is discussed. Volunteers given live vaccine showed a 2.2-fold lower incidence of clinical influenza than those given killed vaccine in a natural epidemic 16 months after vaccination.

Live influenza B vaccine in volunteers. A report to the Medical Research Council by their Committee on Influenza and Other Respiratory Virus Vaccines.

In this paper we describe our experience with a. live vaccine made from an influenza type B virus. Type B was chosen for a number of reasorls. We had had no previous experience with it, an attenuated virus with an acceptable passage history was available, and the low incidence of haemagglutination-inhibiting (HI) antibodies in the population was likely to make it easier to find susceptible volunteers than when an A virus was used. In addition, because different antigenic subtypes of influenza B circulate at the saxnel time (Coinmunicable Disease Center Report, 1965) we wished to look at the evidence for cross-protection. We a]so wished to assess the importance of repeated vaccinatiorls, on which some Russian workers lay considerable stress (SmorodintseJv et al., 1965). Previous trials of live influerlza vaccines in Great Britain (in which repeated vaccinations had not been given) had used vaccines made from a 1957 Russian A 2 virus (McDonald et al. 1 962; Andrews et al. 1 966; Beare et al. 1 967). The results showed that attenuated live viruses infected fairly readily when serum antibody was low or absent, that infection was followed by resistance to challenge with the sarne virus, and that there was a significant rise of antibody in a proportion of people.

Serological studies with purified neuraminidase antigens of influenza B viruses

Neuraminidase (N) can be extracted from virus particles of influenza B strains by treatment with trypsin, in a form which is free from the viral HA and has specific immunological activity. The N antigen of B/LEE/40 behaves differently from that of 1965-6 strains in gel diffusion and enzyme inhibition tests with animal antisera raised by infection or by artificial immunization with the homologous or heterologous strains. The frequency and titres of NI antibody detected in human sera by B/LEE antigen are different from those found with antigen from B/Eng/13/65. The latter antibody appears to contribute to the effect of serum HI antibody in protecting volunteers exposed to a deliberate intranasal challenge infection of the B/Eng/13/65 strain.

A comparison of monovalent Hong Kong influenza virus vaccine with vaccines containing only pre-1968 Asian strains in adult volunteers. A report to the Medical Research Council Committee on Influenza and other Respiratory Virus Vaccines.

A total of 1601 adult industrial workers were vaccinated with either monovalent inactivated vaccine of the Hong Kong strain of influenza A virus, or with polyvalent vaccine containing only pre-1968 Asian viruses. Serological investigations on a random sample of volunteers showed that 53/56 (95%) given Hong Kong vaccine developed a significant rise in specific haemagglutination-inhibiting antibody; final titres were 1/48 or greater in 39 (70%) and the GMT (geometric mean titre) was 96.5. After polyvalent Asian vaccine, 40/67 (60%) also produced antibody against Hong Kong virus, but only 21 (31%) had final titres of 1/48 or above, and the GMT rose only to 14.1. An intranasal spray of the Hong Kong vaccine in addition to injected Asian vaccine gave no additional increase in antibody.Each type of vaccine stimulated a recall of pre-existing antibody against Asian viruses. The possible significance of heterologous responses to the two vaccines is discussed.The incidence of clinical influenza in the trial population was sporadic, and the infection rates were too low to allow any accurate estimate of the protective efficiency of the two vaccines.