Immunogenicity in adult males of a Neisseria meningitidis group B vaccine composed of polysaccharide complexed with outer membrane proteins.

Twenty five adult male volunteers were given a vaccine composed of the capsular B polysaccharide non-covalently complexed to serotype 6 outer membrane proteins (OMP) of Neisseria meningitidis. Subjects were divided into three dose groups receiving 50, 100 or 150 micrograms vaccine in aluminium hydroxide in each of three injections spaced 4 weeks apart. Systemic signs/symptoms considered clinically significant were recorded on 6% (4/70) of occasions and were succeeded by withdrawal of two volunteers from the study. Local injection site reactions, mostly mild to moderate, were reported after all vaccinations with one such reaction leading to a third volunteer withdrawing from the study. Geometric mean anti-B responses before immunization and 1 week after the third immunization (9 weeks) were 3.60 and 7.12 micrograms ml-1 in the 50 micrograms group (p less than 0.05) 2.05 and 12.19 micrograms ml-1 in the 100 micrograms group (p less than 0.001), and 3.68 and 14.20 micrograms ml-1 in the 150 micrograms group (p less than 0.001). The anti-B response was predominantly of the IgM isotype and persistence above prevaccination levels was evident for at least 12 months. Anti-type 6 OMP responses were also evidenced with geometric mean multiplicative increases over prevaccination levels at 9 weeks and 6 months of 7.8 and 4.2 for the 50 micrograms group, 11.6 and 5.6 for the 100 micrograms group and 6.8 and 3.4 for the 150 micrograms group. The bulk of this response was of the IgG isotype. Passive protection of mice was achieved with both pre- and post-vaccination (9 weeks; 100 and 150 micrograms groups) pools of sera.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind comparative trial of standard (commercial) and antibody-affinity-purified tetanus toxoid vaccines.

Tetanus toxoid purified by antibody-affinity chromatography, was compared with conventionally purified material in a double-blind trial in 205 healthy blood donors. There was neither any difference in immunogenicity as assessed by enzyme-linked immunoassay nor in side-reactions between the two vaccines. This study confirms that side-reactions to tetanus toxoid are not eliminated by purifying it.

Failure of intranasally administered 4', 6-dichloroflavan to protect against rhinovirus infection in man.

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in tissue culture systems was tested in a double-blind, placebo-controlled volunteer trial for its protective efficacy against experimental rhinovirus infection. Dichloroflavan was administered intranasally as a 5 per cent w/v aqueous suspension (40 mg; 5 times per day) for 5 doses before and 21 doses after intranasal challenge with rhinovirus type 9, a virus type known to be highly sensitive to the drug when tested in tissue culture. A total of 49 volunteers were included in the efficacy analysis. Dichloroflavan did not produce any consistent or significant reduction in clinical or laboratory parameters of infection. Indeed there was some indication that treatment with the drug may have been associated with increased severity of clinical signs and symptoms. Dichloroflavan administered intranasally is not, therefore, of value in the prevention of human rhinovirus infection.

A comparison of the reactivity and immunogenicity of RA 27/3 strain rubella vaccine prepared in WI-38 or MRC5 human diploid cells.

The immunogenicity and clinical reactivity of rubella vaccine derived from WI-38 or MRC5 human diploid cells was compared in 125 seronegative adolescent females. Seroconversion rates, assessed by single radial haemolysis testing of paired pre- and post-vaccination samples exceeded 98% (56/57 and 68/68 vaccinees, respectively) for both vaccines. Quantitative assessment of rubella-specific antibodies in 53 post-vaccination sera by an ELISA technique also failed to reveal any difference in immunogenicity between the vaccines. Assessable calendar records documenting the occurrence of local and systemic signs and symptoms in the four weeks following vaccination were returned by 106 subjects. No important statistically significant difference in parameters of clinical reactivity between the vaccine groups was observed although the incidence of pain at the injection site was found to be significantly higher for vaccinees receiving WI-38 derived vaccine.

Development and persistence of class-specific antibodies in the serum and nasopharyngeal washings of rubella vaccinees.

Serial samples of serum and nasopharyngeal washings were obtained from 43 volunteers given one of four rubella vaccines (HPV77.DE5, RA27/3, To-336, and Cendehill) and from nine naturally infected volunteers. Rubella-specific serum IgG was detected by radioimmunoassay for up to 12 years in all but one vaccinee, and booster responses occurred in 23.3% of vaccinees. Rubella-specific serum IgA was detected in 37 (90.2%) of 41 vaccinees one year after vaccination but in only five (45.5%) of 11 vaccinees tested 10-12 years after vaccination. Low levels of rubella-specific IgM detected by M-antibody capture radioimmunoassay persisted in seven volunteers--four of them HPV77.DE5 vaccinees--four more than one year after vaccination. Rubella-specific nasopharyngeal IgA was detected for up to five years after natural infection or vaccination with RA27/3 but for no longer than three years among Cendehill, HPV77.DE5, and To-336 vaccinees. Nasopharyngeal IgG antibodies were detected less frequently and at lower levels.

Intranasal lymphoblastoid interferon ("Wellferon") prophylaxis against rhinovirus and influenza virus in volunteers.

Purified lymphoblastoid interferon (HuIFN-alpha) or placebo was self-administered intranasally by volunteers using a spray device three times daily for four and one-third days beginning one day before virus challenge. Each subject received a total dose of 35.1 Mu of interferon (IFN) administered in 13 equal doses of 2.7 Mu. Doses were administered in a volume of 0.2 ml (0.1 ml to each nostril). The first group received human rhinoviruses types 9 and 14. There were no significant colds in 19 volunteers receiving IFN and 7 in 23 volunteers receiving placebo (p less than 0.05). Serological responses and/or recovery of challenge virus were obtained in 14 (74%) recipients of IFN and in all 23 recipients of placebo (p less than 0.05). Mean daily and total clinical scores and mean daily and total nasal secretion weights were significantly greater in those receiving placebo than in those given IFN. The second group received influenza virus A/Eng/40/83. There were 4 significant illnesses in 13 volunteers receiving IFN and 10 in 17 volunteers receiving placebo (p greater than 0.05). Serological responses and/or recovery of challenge virus were obtained in 11 volunteers receiving IFN and 14 volunteers receiving placebo. Mean daily secretion weight and mean clinical scores were lower in those given IFN than in those given placebo - the differences were significant for clinical score on 2 days. The results suggest that IFN prophylaxis was less effective against influenza A than against rhinovirus.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of oral 4',6-dichloroflavan to protect against rhinovirus infection in man.

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in vitro, was tested in a double-blind placebo controlled volunteer trial for its protective effect against experimental rhinovirus infection. Dichloroflavan was given orally (1 mg/kg, 3 times per day) for 3 doses before, and 13 doses after intranasal challenge with rhinovirus type 9, a type known to be highly sensitive in tissue culture. A total of 63 volunteers were included in the analysis for efficacy. Dichloroflavan did not produce any consistent or significant reduction in quantitative clinical or laboratory evidence of infection, and there was no apparent negative correlation of such data with drug concentrations in plasma. It is concluded that administration of dichloroflavan in the oral formulation tested is not of value in the treatment of human rhinovirus infection.

A single-blind, placebo-controlled comparison of the reactivity and antigenicity of trivalent oral poliomyelitis vaccine prepared in monkey kidney or human diploid cell substrates.

Vaccination with a single dose of trivalent oral poliomyelitis vaccine elicited fourfold or greater antibody responses to one or more poliomyelitis virus types in 59% of volunteers (16/27) receiving vaccine prepared from virus grown in monkey kidney cells and in 69% of volunteers (16/23) receiving vaccine prepared from virus grown in MRC5 human diploid cells. Type for type the antibody titres and percentages of volunteers responding to the two vaccines were broadly equivalent. The clinical reactivities of both vaccines were similar to that of a placebo in terms of the overall incidence, duration and severity of reactions. The nature of the reactions observed did, however, vary, in that headaches were more frequently reported by recipients of vaccine prepared from virus grown in monkey kidney cells. This difference was not, however, statistically significant.

A comparative clinical study of Adsorbed Tetanus Vaccine and Adult-type Tetanus-Diphtheria Vaccine.

A limited assessment of immunity to diphtheria revealed that only 44.8% of adults had protective levels (greater than 0.01 U/ml) of diphtheria antitoxin in their sera. In the light of this information, it was decided to assess the suitability of Adult-type Tetanus-Diphtheria Vaccine as a replacement for Adsorbed Tetanus Vaccine in occupational health schemes. A comparative study of these vaccines showed that a single dose of each produced an equivalent rate and level of tetanus antitoxin responses. Adult-type Td Vaccine elicited more than fourfold increases of diphtheria antitoxin in 76% of vaccinees. No statistically significant differences were observed in the clinical reactivity of the vaccines under test. However, the combined vaccine caused a slightly higher incidence of local reactions (pain, redness and swelling) while recipients of Adsorbed Tetanus Vaccine more frequently experienced pain.