[Immunogenicity of a hepatitis B vaccine obtained by genetic recombination and containing products of S and pre-S2 genes]. / Immunogénicité d'un vaccin contre l'hépatite B obtenu par recombinaison génétique et contenant les produits des gènes S et pré S2.

Immunization against hepatitis B by means of a vaccine obtained by genetic recombination on chinese hamster ovary cells was attempted in 32 adult subjects. The HBs antigen was purified from the culture supernatant and contained S and pre S2 genes products. Three 20 micrograms doses were injected intramuscularly at intervals of one month. Anti-HBs seroconversion levels and the geometrical mean of antibodies were slightly higher than those observed with plasma vaccines or genetically engineered yeast-derived vaccine. Antibodies directed against HBs appeared more rapidly and at a higher titre. Anti-pre S2 antibodies were detected after the third injection in 84 per cent of the subjects vaccinated. This recombinant hepatitis B vaccine prepared from chinese hamster ovary cells will probably be as effective as the first generation vaccines obtained by purifying the HBs antigen obtained from the blood of asymptomatic carriers.

Hepatitis B virus type 2 infection in France.

Hepatitis B type 2 infection was observed in 96 French soldiers. A recent stay overseas was reported by 65% of them and an HBsAg chronic carrier state was observed in eight individuals. Anti-pre-S1 and anti-pre-S2 antibodies were not detected after recovery, but HBV DNA was detected in 58% of sera tested.

Mapping of linear B-cell epitopes of hepatitis B surface antigen.

Eight monoclonal antibodies directed against the surface protein of hepatitis B virus (HBV) were tested using an epitope-mapping system (Pepscan) for characterizing antigenic domains. Four different amino acid sequences corresponding to linear epitopes were identified: one in pre-S1 corresponding to the sequence 29-36, two in pre-S2 corresponding to overlapping sequences 134-141 and 137-144, and one in the S region of the protein corresponding to the amino acid sequence 117-126.

Anti-pre-S2 antibodies in natural hepatitis B virus infection and after immunization.

Anti-pre-S2 antibodies were detected by enzyme-linked immuno-absorbant assay using a synthetic peptide analogue of pre-S2 protein, in different groups of hepatitis-B-infected subjects, including patients presenting with cirrhosis and liver cancer, and also in infants immunized with hepatitis B vaccine. Anti-pre-S2 antibodies were not detected in hepatitis B surface antigen (HBsAg) chronic carriers, including patients with cirrhosis or primary liver cancer. Anti-pre-S2 antibodies were not detected in HBsAg-positive sera during the early phase of acute hepatitis. They were only noted upon recovery, when anti-HBs antibodies are detectable at the same time as HBsAg. After recovery, anti-pre-S2 antibodies were noted in 57% of test sera and were still detectable in 16% of anti-HBs-positive sera obtained years after HBV infection. Anti-pre-S2 antibodies were detected in 70% of infants immunized with 2 or 5 micrograms doses of Hevac B Pasteur vaccine, confirming that this vaccine contains pre-S2 antigen. Anti-pre-S2 detection was correlated with the anti-HBs antibody titre.

Prevalence of hepatitis C virus infection in Africa: anti-HCV antibodies in the general population and in patients suffering from cirrhosis or primary liver cancer.

Anti-hepatitis-C-virus (anti-HCV) antibody was tested for in sera from 410 adults living in Tunisia, Senegal, Burundi and Madagascar, and in 209 Tunisian and Senegalese patients suffering from liver diseases. Anti-HCV antibodies were detected in 4.2% of the adult population from Africa, in 51% of patients suffering from liver cirrhosis and in 37% of patients suffering from primary liver cancer. However, higher proportions of anti-HCV antibodies were detected in HBsAg+ patients than in HBsAg- patients. To assess the role of HCV in the development of both cirrhosis and primary liver cancer, a confirmation test is needed.

Antibody response to preS1 in hepatitis-B-virus-induced liver disease and after immunization.

Antibodies to the pre-S1-encoded sequence of hepatitis B virus (HBV) envelope were detected by ELISA using a synthetic peptide analogue of preS1 proteins, in different groups of HBV-infected subjects and also in hepatitis B vaccine recipients. Such antibodies were specifically found in only 1% of HBsAg chronic carriers including patients with cirrhosis and primary liver cancer. Anti-preS1 were detected in patients with acute hepatitis; in 13% of the HBsAg+ sera obtained before recovery and in 37% of the sera obtained after recovery. Anti-preS1 antibodies were detected in recipients of a plasma-derived vaccine, but not in those receiving a recombinant vaccine. The results indicate that anti-preS1 is an earlier serum marker of HBV clearance than anti-preS2 and anti-S antibodies.

Simultaneous injection of hepatitis B vaccine with BCG and killed poliovirus vaccine.

In most developing countries, hepatitis B virus is endemic and prevention has to be carried out early in life and on a mass scale. In these regions, simultaneous administration of multiple antigens is normal practice. We have therefore investigated the interaction of hepatitis B vaccine with BCG and inactivated polio vaccine. The serological antibody response to poliovirus and HBsAg as well as the cellular immune response to tuberculin post BCG immunization were assessed. The immune responses to HBsAg, BCG and polio vaccines injected simultaneously were comparable to those observed after separate administration of each vaccine. Moreover, no increase of adverse reactions was noted. Results confirmed that HB vaccine could be introduced into the WHO expanded programmes on immunization without impairing the expected protective efficacy against the targeted vaccine-preventable diseases.

Comparative immunogenicity in children of mammalian cell-derived recombinant hepatitis B vaccine and plasma-derived hepatitis B vaccine.

Three doses of hepatitis B vaccine were given at 2, 4 and 9 months of age to 220 Senegalese infants living in the Dakar area of Senegal. Half of the infants received 5 micrograms plasma-derived hepatitis B vaccine (Hevac B) and the remainder 20 micrograms mammalian cell-derived recombinant hepatitis B vaccine (GenHevac B). Both vaccines contain S and pre-S2 encoded proteins; however, the recombinant vaccine had a much higher pre-S2 content than the plasma-derived vaccine. Adverse reactions to both vaccines were limited to mild and transient soreness at the injection site. Fever was reported in 14-21% of the infants and was likely to be related to DTP-polio vaccine which was given simultaneously. After the two first doses, seroconversion rates and geometric mean titres of anti-HBs were higher in infants receiving the recombinant vaccine than in infants receiving the plasma-derived vaccine. After completion of vaccination, all infants in both groups had protective levels of anti-HBs antibodies. The recombinant vaccine induced more rapidly antibodies directed against S and pre-S2 epitopes. Anti-pre-S2 antibodies were detected after the first injection of GenHevac B and only after the third injection of Hevac B. From the data, GenHevac B vaccine is expected to be as effective as Hevac B vaccine for controlling hepatitis B infection.

Hepatitis B surface antigen reactivity in man due to a new variant of hepatitis B virus.

A new type of hepatitis B virus (HBV) infection has been encountered in Senegalese infants and French adults characterized by serum hepatitis B surface antigen (HBsAg) without antibodies to the core antigen (anti-HBc). As the infection is not associated with the presence of the e antigen, it differs from HBV in its core antigen. After the loss of HBsAg, neither anti-HBc nor antibodies to HBsAg (anti-HBs) become detectable. This new infection (called HBV2 as opposed to the classical HBV1 infection) was found in infants with anti-HBs, either naturally acquired or produced by immunization against HBV. The use of monoclonal anti-HBs antibodies showed that two epitopes of HBV1 surface antigen could be detected in HBV2-positive sera. HBV DNA sequences could only be found in one of 15 HBV2-infected children using a DNA-DNA hybridization procedure; low levels of HBV DNA were also detected in 58% of the HBsAg-positive adult sera tested. If this new infection, apparently related to HBV1, is shown to cause chronic liver disease, hepatitis B vaccine should also contain surface antigen from HBV2.

HBsAG positive reactivity in man not due to hepatitis B virus.

A viral infection characterised by serum HBsAg positivity with serum anti-HBc negativity has been encountered in Senegal. The infection is not associated with the presence of HBeAg, so it differs from hepatitis B virus in its core antigen, but the surface antigen of the two viruses share some epitopes. After the loss of HBsAg, neither anti-HBc nor anti-HBs becomes detectable. Anti-HBs, naturally acquired or produced by immunisation, does not protect against this new infection. Chronic carriage occurs. If this new infection is confirmed to cause chronic liver disease, hepatitis B vaccine should include surface antigen from the new virus.