Rapid and frequent induction of protective immunity exceeding UK recommendations for healthcare settings by MF59-adjuvated hepatitis B vaccine.

The ability of three doses of a novel MF59-adjuvanted hepatitis B virus (HBV) vaccine containing surface and pre-S2 antigens given at 0, 1, and 6 months to induce levels of HBV surface antibody (sAb) > or = 100 mIU/ml was compared with a UK licensed alum-adjuvanted yeast-derived HBV vaccine in HBV-naive healthcare workers (HCWs). One month after second immunization with HBV/MF59, 100% of HCWs had sAb > or = 100 mIU/mL, compared with only 11% and 85% after two or three immunisations with Engerix-B. The sAb GMT of the Engerix B immunised group remained below 100 mIU/mL until month seven, (compared with month one for HBV/MF59), and was 123-fold lower at this time (208,561 vs. 1,686 mIU/mL). In our subjects HBV/MF59 vaccine rapidly induced sAb to levels far in excess of those recommended by the Department of Health for high-risk situations (e.g. HCWs and patients on dialysis). It has the potential for shorter schedules and reduced need for serology and boosters.

Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants: A randomized controlled trial.

CONTEXT: Neisseria meningitidis is a common cause of meningitis and septicemia in infants worldwide. Whether a meningococcal C conjugate vaccine protects infants against the serogroup C strain is unknown. OBJECTIVES: To determine whether a meningococcal C conjugate vaccine is safe and immunogenic and induces immunologic memory in infants. DESIGN: Single-center, double-blind, randomized controlled trial in 1995 and 1996. SETTING: Community, Oxfordshire, England. PARTICIPANTS: One hundred eighty-two healthy infants. INTERVENTIONS: Participants were randomly assigned to receive vaccination with 0. 5-mL doses of 1 of 2 lots of meningococcal C conjugate vaccine (groups 1 and 2; n=60 in each group) or a hepatitis B control vaccine (group 3; n=62), administered with routine immunizations at 2, 3, and 4 months of age. Approximately half of each group received meningococcal C conjugate vaccine and half received plain meningococcal polysaccharide vaccine (MPS) at 12 months of age. MAIN OUTCOME MEASURES: Serum antibodies to meningococcal C polysaccharide, assayed by enzyme-linked immunosorbent assay, and serum bactericidal activity (SBA), at 2, 3, 4, 5, 12, and 13 months of age; local and systemic reactions, recorded for 6 days after each vaccination, compared by intervention group. RESULTS: Meningococcal C conjugate vaccine was well tolerated. After 3 doses, children in groups 1 and 2 achieved significantly higher meningococcal C IgG geometric mean concentrations (21 and 17 U/mL, respectively, vs 0.20 U/mL; P<.001) and SBA titers (629 and 420, respectively, vs 4.1; P<. 001) than controls. At 12 months, antibody concentrations had decreased in all groups but remained significantly higher in children vaccinated with meningococcal C conjugate vaccine (SBA, 24 and 16 in groups 1 and 2, respectively, vs 4.2 in group 3; P<.001). Following vaccination with MPS at 12 months of age, SBA in the meningococcal C conjugate vaccine group was significantly higher than in controls (SBA, 789 vs 4.5; P<.001). CONCLUSIONS: Our data indicate that meningococcal C conjugate vaccine is safe and immunogenic and results in immunologic memory when given with other routinely administered vaccines to infants at 2, 3, and 4 months of age. JAMA. 2000;283:2795-2801

Immunogenicity and reactogenicity of a group C meningococcal conjugate vaccine compared with a group A+C meningococcal polysaccharide vaccine in adolescents in a randomised observer-blind controlled trial.

This study evaluated the immunogenicity and reactogenicity of a group C meningococcal conjugate vaccine (MenC) compared with a group A+C meningococcal polysaccharide vaccine (MenPS) in healthy adolescents. Subjects were randomised to receive one dose of either MenC (n=92) or MenPS (n=90). Group C meningococcal IgG antibody concentrations and bactericidal titres were higher in the MenC group than the MenPS group at 1 month (22.8 U/ml vs 4.0 U/ml, p<0.001, and 87 vs 20, p<0.001, respectively) and 12 months (6.1 U/ml vs 3.0 U/ml, p<0.001, and 81.3 vs 20.2, p<0.001, respectively). No differences in post immunisation reaction rates were noted between the two vaccinated groups. This study demonstrated the safety and enhanced immunogenicity of the candidate meningococcal conjugate vaccine as compared with the licensed polysaccharide vaccine in adolescents.

Prevalence of hepatitis A, B and C in the Flemish population.

Viral hepatitis is a serious health problem throughout the world. No recent prevalence data on hepatitis A, B and C were available for the population in Flanders, Belgium. For this reason, a sero-epidemiological study was undertaken in 1993-1994 in a sample of the general population. The purpose of this study was to obtain a clear picture of the prevalence of hepatitis A, B and C. Between April 1993 and February 1994, 4,058 blood samples were drawn and collected in 10 hospitals in Flanders. The study group was representative for the Flemish population. For hepatitis A a seroprevalence of 55.1% was found. In the non-Belgian residents the HAV prevalence was significantly higher than in Belgians (62% versus 52%; chi2 = 8.05; p = 0.005). For hepatitis B. 9.9% of the study group showed serological evidence of hepatitis B markers: 6.9% of the participants was positive for anti-HBs/anti-HBc, 0.7% appeared to be HBsAg positive and 3.5% was solely anti-HBs positive. The prevalence of HBV markers in Belgians was 6.9%, significantly lower compared to the 13.4% among non-Belgians (chi 2 = 14.05; p = 0.00018). 4055 serum samples were analysed for hepatitis C serology by second generation anti-HCV tests. Anti-HCV was detected in 0.87% of the serum samples. No statistically significant difference was found in HCV prevalnece between Belgians and non-Belgians. Results of this study should help policy makers in their decisions on the most appropriate hepatitis A and B vaccination strategy and on the most effective prevention strategy for hepatitis C.

Immunogenicity and safety of a new inactivated hepatitis A vaccine in a comparative study.

A multicentre, controlled, randomised, open, comparative trial including 839 healthy adult volunteers was carried out in order to compare the immunogenicity and reactogenicity of two vaccines against hepatitis A virus (HAV) during primary immunization and after booster injection. The first vaccine was produced by Pasteur Mérieux (PM), and the second vaccine by Smith-Kline Beecham (SKB). The vaccination schedule consisted of 2 doses (months 0, 6) for PM and 3 doses (months 0, 1, and 6) for SKB. Two weeks after the first dose, the seroconversion rates among initially HAV seronegative subjects (n = 608) were 93.4% and 76.1% for the PM and SKB vaccines, respectively, the corresponding geometric mean titres (GMTs) were 59.0 mIU/ml versus 30.8 mlU/ml (modified RIA HAVAB assay, Abbott Laboratories). Two months after the beginning of immunization (one dose versus two doses) the GMTs were 138.4 and 161.6 mlU/ml, respectively. At month 7, the seroconversion rates were 100% for both vaccines, and the GMTs were 4,189 and 3,163 mlU/ml, respectively. After the first dose of vaccine, 24.6% and 19.6% of the PM and SKB vaccines reported local reactions. The rates for systemic reactions were 27.2% and 25.0%, respectively. Lower rates for local and systemic reactions were seen after booster injections and statistical differences were not observed between the two vaccines. The study also demonstrated that vaccination was as well tolerated in subjects with anti-HAV antibodies as in HAV seronegative subjects. Logistic regression analysis revealed a significant vaccine effect on seroconversion rates only at week 2 (P < 10(-4). The same conclusions were drawn from the analysis of GMT by multivariate regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-response to a recombinant pre-S2-containing hepatitis B vaccine: association with the HLA-system.

In this study, the immunogenicity of a recombinant pre-S2 containing hepatitis B vaccine was determined in a cohort of 147 homosexual men. Both seroconversion rate and geometric mean titers indicated that pre-S2 was less immunogenic than HBsAg. Forty-eight subjects, including nine non-responders and seven high-responders to HBsAg, were tested for HLA Class I and II antigens to study a possible association between HLA-type and non-response. Both HLA-B8 and HLA-DR3 were clearly overrepresented in non-responders to HBsAg. Non-response to pre-S2, observed in 7/9 non responders and 6/39 responders to HBsAg, was not associated with any of the tested HLA markers.

Immunological parameters during treatment with ditiocarb (Imuthiol).

OBJECTIVES: To examine the effect of ditiocarb (DTC) treatment on immunological parameters of HIV infection. Immunophenotyping included CD4+ T-cell counting and the analysis of activation markers on CD8+ T cells. Anti-CD3-induced proliferation and anti-CD3-mediated cytotoxicity were monitored as indexes of T-cell function. In addition to the clinical evolution, HIV antigen and anti-p24 levels were monitored during treatment. DESIGN: In this double-blind, placebo-controlled study, 50 HIV-seropositive patients belonging to all clinical disease stages were randomized to treatment with DTC or placebo and followed for 4 months. METHODS: Immunophenotyping on whole blood was performed by flow cytometry, using combinations of anti-CD8 with anti-CD4, anti-HLA-DR, anti-CD38, anti-CD45RO and anti-CD57. Patient lymphocytes were freshly assayed for cytolytic capacity against OKT3-coated targets. T-cell proliferation was measured after 3 days of OKT3-stimulation. RESULTS: No effect was observed on CD4 and CD8+ T-cell counts or on CD8+ T-cell activation markers, except for a selective increase in HLA-DR expressing CD8 cells in the DTC-treated group. Decline in anti-CD3-induced T-cell proliferation and rise in anti-CD3-mediated T-cell cytotoxicity were observed in the DTC and placebo groups. No effect on HIV antigen and anti-p24 antibody titres was observed. The incidence of clinical complications was similar in each group. CONCLUSION: No beneficial immunomodulatory effect of DTC was demonstrated.

Subset markers of CD8(+) cells and their relation to enhanced cytotoxic T-cell activity during human immunodeficiency virus infection.

Using fresh whole blood or isolated lymphocytes, the activity of in vivo generated cytotoxic T-lymphocytes (CTL) was measured as the OKT3-specific lysis of HL-60 targets, in a cross-sectional study of 53 HIV (+) patients. CTL activity in the entire HIV(+) group was two to three times higher than in HIV(-) controls, with WHO stage 3 (=pre-AIDS) patients showing the highest cytolytic function. The whole-blood CTL assay was validated and its practical and theoretical advantages are discussed. Within the CD8(+) cells, the number and proportion of the CD45RO(+) "memory" subset were significantly increased in HIV(+) subjects. The HLA-DR(+) subset rose most spectacularly in the asymptomatic stage of the infection, while the CD38(+) subset was the only one still significantly rising between the pre-AIDS and the AIDS stage. CTL activity was most closely correlated with T8 cells expressing the CD38 marker. In the context of CTL, CD38 thus seems to reflect activation rather than immaturity. Lymphocytes from HIV(+) subjects with a high OKT3-specific lytic capacity also destroyed normal lymphoblasts to a significant extent, pointing to their possible involvement in an autodestructive process. Our data thus suggest the importance of T8 cytolytic function and/or T8 subtyping in the immunopathogenesis and the prognosis of HIV infection.

Hepatitis B: transmission by sexual contact and needle sharing.

In the Western world most cases of hepatitis B virus (HBV) infection are acquired through sexual intercourse and through needle sharing by intravenous drug users (IVDU). The major risk factors for HBV infection in homosexual men include the number of sex partners and receptive anal intercourse. In heterosexuals, this risk also rises with an increasing number of sex partners. IVDU consistently show the highest HBV infection rates in Europe and North America, presently accounting for 25 to 50% of all hepatitis B cases. Infection with the human immunodeficiency virus affects the course of HBV infection as well as the immunological response to hepatitis B vaccines. Thus, in the industrialized world, interventions against HBV infection should primarily be targeted to homosexual men, heterosexuals with multiple partners, and IVDU.

Protective efficacy of a recombinant DNA vaccine against hepatitis B in male homosexuals: results at 36 months.

An open study with a recombinant DNA yeast-derived hepatitis B vaccine (YDV) was carried out in homosexual men to assess the protective efficacy of this vaccine. A total of 278 seronegative volunteers were enrolled to receive three intramuscular doses of either 20 or 40 micrograms at months 0, 1 and 6. Serum specimens were taken at various times up to 36 months; relevant information regarding the occurrence of other sexually transmitted diseases (STDs) and sexual behaviour was also collected annually. One month after the third injection, the seroconversion rate in both groups was 99%. The geometric mean anti-HBs titre at this time was higher for subjects receiving 40 micrograms doses although a similar percentage of the vaccinees had titres greater than 10 mIU ml-1 in both groups. Compared with a historical control group in which the annual incidence of hepatitis B infection was 12%, only two vaccinees developed markers of infection during the immunization period and none thereafter. While an important increase in the use of condoms was noted during the 1984-87 study period and the incidence of some STDs declined, these changes could not solely account for the decrease in hepatitis B infection in the study population.

Vaccination against hepatitis B in homosexual men. A review.

Homosexual men are at increased risk for infection with hepatitis B virus (HBV). Both plasma-derived and recombinant deoxyribonucleic acid vaccines have been shown to induce long-standing protective immunity in this population. However, non-responders and weak responders to HBV vaccine have recently become a problem among homosexual men because of an impaired antibody response due to previous infection with human immunodeficiency virus. In addition, human immunodeficiency virus infection predisposes persons to the development of a HBV carrier state following HBV infection. Vaccination still remains the most effective tool for preventing hepatitis B in homosexual men, although recent behavioral changes have apparently resulted in a decreased incidence of HBV infection among this group.

Risk factors for infection with human immmunodeficiency virus among European expatriates in Africa.

The pattern of cases of AIDS in Belgium suggests that Europeans infected with human immunodeficiency virus (HIV) acquired the infection in Africa. The prevalence of infection was assessed in Belgian advisers and European expatriates and risk factors for infection defined in a case-control study of expatriate men. Fifteen (1.1%) of 1401 Belgian advisers working in Africa and 41 (0.9%) of 4564 European expatriates living in Africa, were positive for antibody to HIV in a voluntary screening programme in Belgium. Among subjects with antibody to HIV the ratio of men to women was 3:1. These subjects did not have a history of intravenous drug abuse or blood transfusion and only one was homosexual. In a case-control study of 33 expatriate men who had antibody to HIV and 119 controls the men with antibody reported significantly more female sexual partners, who were more commonly local; and significantly more sexual contact with prostitutes in Africa. They had a significantly higher prevalence of history of sexually transmitted disease and had received significantly more injections by unqualified staff in Africa during the previous five years. No specific sexual practices were associated with having antibody to HIV. After multivariate analysis sexual contact with local women (adjusted odds ratio 14.7; 95% confidence interval 2.81 to 76.9), sexual contact with prostitutes (adjusted odds ratio 10.8 (1.6 to 71.9), and injections by unqualified staff (adjusted odds ratio 13.5 (3.7 to 49.8) remained independent risk factors for infection. European expatriates in Africa were at increased risk from infection with HIV and were a means of introducing HIV into the heterosexual population in Europe. Transmission from women to men by vaginal intercourse seemed to be the most probable route of infection.

Immunogenicity and tolerance of a yeast-derived hepatitis B vaccine in homosexual men.

A yeast-derived recombinant DNA vaccine against hepatitis B was administered to 314 active homosexual men lacking serum markers for hepatitis B virus. Volunteers were vaccinated intramuscularly in the deltoid region at 0, 1, and 6 months with either a 20- or 40-micrograms dose per injection. Serologic tests for syphilis and human immunodeficiency virus were positive in 3.2% and 2.0%, respectively. The overall seroconversion rates for anti-HBs were 35%, 97%, and 98% after the first, second, and third injection, respectively. The geometric mean titres of anti-HBs antibodies at 7 months were 955 IU/l and 2541 IU/l, for the 20 and 40 micrograms doses, respectively. Among 183 completely vaccinated subjects, 97% had an anti-HBs titre greater than 10 IU/l. Tolerance of the vaccine was excellent. Among the 183 subjects followed up for at least 7 months, two volunteers developed HBsAg and anti-HBc within one month of the first vaccine injection and one anti-HBc just before the third dose of vaccine. However, no subject experienced clinical hepatitis or ALT elevations.