M. Just

A single vaccination with an inactivated hepatitis A liposome vaccine induces protective antibodies after only two weeks

In the near future an inactivated hepatitis A vaccine will be commercially available. The recommended vaccination schedule will include at least two vaccinations 1 month apart. Giving two doses of vaccine on the same day in one injection results in protection after 2-4 weeks dependent on the adjuvant used. Hepatitis A virus incorporated into liposomes proved to be a suitable formulation in term of rapid seroconversion, high level of mean antibody content and low reactogenicity.

Virosomes as carriers for combined vaccines

Immunopotentiating reconstituted influenza virosomes (IRIV) are liposomes which carry the two glycoproteins of the influenza virus on their surface. A hepatitis A vaccine using IRIV as carrier has very good immunogenicity and is well tolerated. The objective of this study was to produce a fivefold combined vaccine against hepatitis A and B, diphtheria, tetanus and influenza A/B, and to show that in principle IRIVs can serve as carriers for multiple antigens which have good immunogenicity and are well tolerated. A total of four studies were carried out. Either the combined vaccine or the corresponding adequately tested alum-adsorbed single vaccines were tested for reactogenicity and immunogenicity in young adults. A hepatitis A and B combination on an IRIV base showed the same immunogenicity and toleration as the single vaccines. However, with the simultaneous coupling of all five vaccines on the same IRIV or the binding of Di-Te and HAV on different IRIVs there was a suppression of the humoral immune response against HAV (p = 0.03). The possibility that epitope-specific suppression had occurred could be ruled out. The suppression of the response against HAV could be circumvented by halving the quantity of Di-Te antigen in the combined vaccine so as to avoid antigenic competition. Surprisingly, the immunogenicity of Di-Te vaccination in the combination proved superior to that of a separate vaccination. All vaccinations were well tolerated.

Persistence of antibodies after immunization with a recombinant yeast-derived hepatitis B vaccine following two different schedules

Four years after vaccination of healthy adults with either a recombinant yeast-derived (YDV) or plasma-derived (PDV) hepatitis B vaccine, the persistence of antibodies to hepatitis B surface antigen (anti-HBs) was examined. Subjects received three 20 micrograms doses in the deltoid region according to either a 0, 1, 6 month or 0, 1, 2 month vaccination schedule, with a 20 micrograms booster dose of YDV administered at month 12 for subjects on the second schedule. The recombinant vaccine was found to be immunologically comparable to the PDV, with anti-HBs persisting equally in both groups.

SEPARATION OF RUBELLA IgM, IgA, AND IgG ANTIBODIES BY GEL FILTRATION ON AGAROSE

Identification of the immunoglobulin classes of rubella antibodies is the only reliable tool for the diagnosis of a recent primary infection with rubella within 6-8 weeks of infection. Gel filtration permits the separation of IgM and IgA antibodies, both characteristic for a recent infection, from persistent rubella IgG antibody (which indicates pre-existing immunity). Gel filtration on agarose offers advantages over the other methods for separating immunoglobulin classes. Fractionation of specific rubella antibodies is important not only in all cases where a serum sample was taken too late and a rise of antibody titre missed, but also in cases with significant antibody rise to distinguish a secondary immune response after rubella reinfection.

Immunisation trials with live attenuated cytomegalovirus TOWNE 125

SummaryTrials with live cytomegalovirus (TOWNE 125 strain), which was attenuated by 125 passages exclusively on WI-38 cells, were done in adult volunteers. No virus take occured after oral/nasal application. When 103 TCD50 was given intramuscularly an IgG antibody response was detected at four weeks in all of ten volunteers tested by immunofluorescence; an IgM response was found in seven. Only mild local side-effects and relative lymphocytosis were observed. No virus excretion was found. Many questions remain to be answered by further trials before a cytomegalovirus vaccine can be given to adolescent girls.ZusammenfassungBei erwachsenen Freiwilligen wurden Immunisierungsversuche mit lebenden Zytomegalieviren, welche durch 125 Passagen ausschließlich auf WI-38 Zellen attenuiert worden waren (TOWNE 125 Stamm), durchgeführt. Orale/nasale Applikation induzierte keine Antikörperbildung. Fluoreszierende IgG-Antikörper konnten bei allen zehn sero-negativen Probanden, welche die attenuierten Zytomegalieviren in einer Dosis von 103 TCD50 intramuskulär erhielten, vier Wochen nach Immunisierung gefunden werden. Zum Auftreten von IgM-Antikörpern kam es bei sieben der zehn Sero-Negativen. Klinisch traten nur geringfügige Lokalreaktionen und eine relative Lymphozytose auf. Es konnte keine Virusausscheidung nachgewiesen werden. Verschiedene bis jetzt noch ungeklärte Fragen müssen zuerst durch weitere „Impfversuche“ an Freiwilligen geklärt werden, bevor an eine generelle Durchimpfung weiblicher Adoleszenten gegen Zytomegalie gedacht werden kann.

Time course of hepatitis A antibody production after active, passive and active/passive immunisation: The results are highly dependent on the antibody test system used

Two commercially available automated test systems for hepatitis A antibody, HAVAB IMX (Abbott) and ENZYMUN Anti-HAV (Boehringer) were evaluated in a study of active, passive and active/passive immunisation against hepatitis A. The inactivated hepatitis A vaccine Epaxal Berna and the hepatitis A immunoglobulin preparation Globuman were products of the Swiss Serum and Vaccine Institute. Although both hepatitis A antibody test kits were standardised with the same international WHO standard hepatitis A immunoglobulin preparation, divergent results were obtained for the level of circulating hepatitis A antibody after vaccination. One month after the vaccination the mean geometric antibody titres were 315 mIU/ml after active, 253 mIU after active/passive and 22 mIU after passive immunisation when measured with the Enzymun assay. In the same sera 70 mIU/ml after active, 60 mIU after active/passive and 18 mIU after passive immunisation could be detected with the IMX test. Antibody avidity studies could not explain the differences obtained by the two test methods. The neutralization test is the standard method for the estimation of protection against hepatitis A. This test is not suitable for large series of serum samples, and enzyme immunoassays are indispensable for vaccination studies. To be suitable for monitoring antibody development in phase I and II clinical trials as well as in postmarketing studies, EIA tests for hepatitis A antibodies must be commercially available and of known sensitivity. The Enzymun anti-HAV test developed by Boehringer Mannheim (Germany) offers the possibility to measure antibody titres around the protective level of 20 mIU/ml which is reached by the passive immunisation with immunoglobulin preparations or within two weeks after active vaccination with an inactivated hepatitis A vaccine. The Abbott IMX test system is more useful for the detection of natural infections by the hepatitis A virus.

Interference between strains in live virus vaccines II: combined vaccination with varicella and measles-mumps-rubella vaccine

A combined vaccine against varicella and measles-mumps-rubella made by mixing two commercially available products (Varilrix and Pluserix SK-RIT) has proved to be only partially successful in early trials. Although the seroconversion rates with the MMR components were comparable with those usually achieved, the varicella take was depressed to 77%. A new low dose measles-mumps-rubella vaccine was prepared in which the measles virus content was reduced to 1/5 and the mumps virus content to 1/8. Commercial varicella vaccine was added to the low dose MMR vaccine. The seroconversion rates for measles was 98.2%, for mumps 100%, for rubella 99.4% and for varicella 98%. This product seemed to be well balanced in respect of a possible interference between the four different virus vaccine strains.

Effects of interferons on immune response to a synthetic peptide malaria sporozoite vaccine in non-immune adults

A Plasmodium falciparum sporozoite vaccine, composed of a synthetic dodecapeptide (NANP)3 coupled to tetanus toxoid (TT), was injected, at weeks 0 and 8, into non-immune volunteers in two randomized double-blind placebo-controlled trials. In the first trial, 37 volunteers received the vaccine simultaneously with placebo (group 1), 0.5 x 10(6-) (group 2), or 1.5 x 10(6) U (group 3) of recombinant human interferon-alpha (= IFN-alpha). In the second trial, 35 other volunteers received the vaccine with placebo (group 4), 0.25 x 10(6) (group 5), or 1.0 x 10(6) IU (group 6) of interferon-gamma (= IFN-gamma). Immunizations were well tolerated and resulted in seroconversion rates (greater than or equal to 4-fold increase of antibody titre in immunofluorescence or enzyme-linked immunosorbent assays) of 67-100% of volunteers. IFN-alpha significantly enhanced the IgG antibody titres in ELISA to malaria peptide.

Interference between strains in live virus vaccines I: combined vaccination with measles, mumps and rubella vaccine

One to four different lots of four commercially available trivalent measles-mumps-rubella vaccines were tested for their efficacy as measured by the induction of antibodies to the three vaccine viruses. All of the products were satisfactory although a 100% seroconversion rate was attained regularly only with rubella vaccine. The live virus in the different measles and mumps vaccine components and especially the relative amounts of measles to mumps virus varied widely. Obviously, the efficacy of a vaccine should not be judged only by the virus content. Of main importance is the further adjustment of the dosage of the interfering vaccine virus strains in relation to their attenuation.

A/New Jersey/76 influenza vaccine trial in seronegative schoolchildren: comparison of a subunit vaccine with a whole-virus vaccine.

SummaryIn the present vaccination trial, 202 seronegative schoolchildren comprising both sexes and aged 11 to 12 years were vaccinated i.m. in the upper arm with either the subunit vaccine at a dosage of 600 CCA or 200 CCA or with a whole-virus vaccine at a dosage of 200 CCA, using the double-blind procedure. Both vaccines were prepared from the strain A/New Jersey/76 (x 5 3a-recombinant). The vaccination was followed four weeks later by a booster injection. In tests of local and systemic reactogenicity, it was found that at both dosages the subunit vaccine caused a low frequency of minor adverse reactions. The whole-virus vaccine was marked by a significantly higher rate of adverse reactions, whether of the local or systemic variety. The whole-virus vaccine had, however, a higher immunogenicity than the subunit vaccine, and due to the relatively high rate of adverse reactions it causes, it is not recommended for the vaccination of seronegative children. Because of its low reactogenicity, the subunit vaccine can be given at higher dosage, and it is a matter for consideration whether a better antibody response might not result from two booster injections.