Safety and efficacy of a recombinant hepatitis E vaccine.

BACKGROUND: Hepatitis E virus (HEV) is an important cause of viral hepatitis. We evaluated the safety and efficacy of an HEV recombinant protein (rHEV) vaccine in a phase 2, randomized, double-blind, placebo-controlled trial. METHODS: In Nepal, we studied 2000 healthy adults susceptible to HEV infection who were randomly assigned to receive three doses of either the rHEV vaccine or placebo at months 0, 1, and 6. Active (including hospital) surveillance was used to identify acute hepatitis and adverse events. The primary end point was the development of hepatitis E after three vaccine doses. RESULTS: A total of 1794 subjects (898 in the vaccine group and 896 in the placebo group) received three vaccine doses; the total vaccinated cohort was followed for a median of 804 days. After three vaccine doses, hepatitis E developed in 69 subjects, of whom 66 were in the placebo group. The vaccine efficacy was 95.5% (95% confidence interval [CI], 85.6 to 98.6). In an intention-to-treat analysis that included all 87 subjects in whom hepatitis E developed after the first vaccine dose, 9 subjects were in the vaccine group, with a vaccine efficacy of 88.5% (95% CI, 77.1 to 94.2). Among subjects in a subgroup randomly selected for analysis of injection-site findings and general symptoms (reactogenicity subgroup) during the 8-day period after the administration of any dose, the proportion of subjects with adverse events was similar in the two study groups, except that injection-site pain was increased in the vaccine group (P=0.03). CONCLUSIONS: In a high-risk population, the rHEV vaccine was effective in the prevention of hepatitis E. (ClinicalTrials.gov number, NCT00287469 [ClinicalTrials.gov].).

Inactivated hepatitis A vaccine: immunogenicity, efficacy, safety and review of official recommendations for use.

There is 10 years of marketing experience with the hepatitis A vaccine Havrix. It is highly immunogenic, provides lasting protection in healthy individuals and generates protective levels of antibodies in patients with chronic liver disease or impaired immunity. Postmarketing surveillance data have confirmed the outstanding safety profile of the vaccine. The timing of the booster dose is not critical to effectiveness, which has advantages for the protection of travelers to regions of high endemicity. The vaccine is effective in curbing outbreaks of hepatitis A and also when administered postexposure, due to rapid seroconversion and the long incubation period of the disease. In intermediate endemic regions, an epidemiological shift in hepatitis A infection has driven the development of universal preventive strategies to be added to the targeting of at-risk groups. Existing official recommendations and future directions for vaccine use are reviewed.

Immunogenicity and reactogenicity of DTPw-HB/Hib vaccine administered to colombian infants after a birth dose of hepatitis B vaccine.

OBJECTIVE: To evaluate, in an open study, the immunogenicity, safety and reactogenicity of a birth dose of hepatitis B vaccine followed by a three-dose course of diphtheria-tetanus whole-cell pertussis-hepatitis B vaccine, extemporaneously mixed with Haemophilus influenzae b (Hib) vaccine. METHODS: At 2, 4 and 6 months of age, a single group of 120 Colombian infants were enrolled in this study to receive a regimen consisting of three doses of the combination vaccine following a dose of hepatitis B vaccine at birth. RESULTS: Seroprotection/vaccine response rates to all vaccine antigens was 98-100% 1 month after completion of the full vaccination course. The vaccine had an acceptable reactogenicity profile and the incidence of reported local and general symptoms decreased with the administration of subsequent vaccine doses. CONCLUSION: The mixed DTPw-HB/Hib vaccine was safe and well-tolerated, with high immunogenicity against all component antigens. Compared with previous studies, reactogenicity did not increase with the additional dose of hepatitis B vaccine given at birth. The DTPw-HB/Hib combination can be used to provide primary vaccination of infants who have already received a first dose of hepatitis B vaccine at birth.

The immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 combination vaccine: results from four phase III multicenter trials across three continents.

This paper presents the results of four separate phase III trials, which assessed the immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 in comparison with licensed Tritanrix-Hep B (GlaxoSmithKline Biologicals) and Hiberix (10 microg PRP), given as separate or mixed injections (3 trials) or with or without hepatitis B vaccine at birth (1 trial). The immunogenicity of DTPw-HBV/Hib 2.5 was non-inferior to the reference vaccine regimen in terms of seropositivity rates. The overall reactogenicity profile of DTPw-HBV/Hib 2.5 was also similar to that of the reference vaccine regimen. These results confirm the previously established immunogenicity and safety of reduced dose PRP conjugated vaccine regimens.

Comparative pre-clinical and clinical experience with oral polio vaccine produced on MRC-5 cells or on primary monkey kidney cells.

The need to avoid using primates has prompted the replacement of primary monkey kidney cells (PMKC) as a substrate for oral polio vaccine (OPV) production. Here, we report on OPV produced on MRC-5 cells using an industrial process capable of producing over 1 billion doses. All serotypes produced on MRC-5 cells proved satisfactory in the monkey and transgenic mice neurovirulence tests. All the type 3 MRC-5 lots tested by Mutant Analysis by PCR and Restriction Enzyme Cleavage (MAPREC) had a 472-C content below the acceptable limit and similar to that of PMKC derived lots. The safety/reactogenicity and immunogenicity profiles following vaccination in infants and children were similar for OPV MRC-5 and OPV PMKC vaccine lots. Excretion rates and prevalence of revertants for the three serotypes following vaccination were also similar for both vaccines. These data support the use of MRC-5 cells as an alternative to PMKC for OPV production.

Immunogenicity and reactogenicity of a combined high dose hepatitis A and hepatitis B vaccine, compared to that of Twinrix in healthy Indian children.

BACKGROUND AND AIMS: Hepatitis A virus (HAV) and hepatitis B virus (HBV) are vaccine preventable important childhood acquired infectious diseases in developing countries. In the changing epidemiology of HAV, the utility of such a vaccine in India needs urgent attention. Further, the efficacy of two versus three dose schedule needs to be assessed to improve compliance. SUBJECTS AND METHODS: One hundred healthy school children, aged 1-15 years were recruited in a randomised open study to receive either vaccination schedule: Group I: combined high-dose hepatitis A and B vaccine to be administered on a 0, 6 month schedule intramuscularly; Group II: to be administered on 0, 1, 6 month Twinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) schedule intramuscularly. The seroconversion (> or =1MIU/ml for anti-HBs antibodies and > or =33MIU/ml for anti-HAV antibodies) and seroprotection (anti-HBs > or =10MIU/ml after the third dose of vaccine) rates were determined at months 1, 2, and 7. RESULTS: The mean age and gender was similar between groups: 7.9+/-2.6 years (range 3-15 years). At month 7 all subjects (100%) in both groups were seropositive for anti-HAV antibodies, Group I had higher anti-HAV titres at months 1 or 2 compared to Group II (P=0.025, P=0.040). Group II developed higher seroprotection rates (month 2, P=0.002, month 6, P=0.003) compared to Group I and higher titres (month 2, P=0.001, month 6 P=0.001) compared to Group I. At month 7, the geometric mean titres (GMTs) were comparable between groups and seroprotection reached 100% in both the groups. The incidence of any symptom per dose analysis reported during a 4-day follow-up period was significantly higher in Group I, 53% (52/98) of the documented doses compared to 37% (54/146) in Group II (P=0.018). CONCLUSION: Twinrix vaccine is safe and highly immunogenic in Indian children. Further study of the high dose vaccine would determine if its two dose regimen is a feasible advantage.

Anamnestic response to administration of purified non-adsorbed hepatitis B surface antigen in healthy responders to hepatitis B vaccine with long-term non-protective antibody titres.

A clinical trial with four groups receiving either 0.6, 3.5, 10 or 20 micro g of purified non-adsorbed hepatitis B surface antigen (HBsAg) was performed to study the kinetics as well as the capacity of the immune memory to respond following exposure to HBsAg in responders to a complete course of hepatitis B vaccine, in whom anti-HBs titres had declined below the seroprotective level. The study population included 64 healthy individuals. All response parameters seropositivity, seroprotection rates, booster response rates and geometric mean titres (GMTs), consistently showed that the immune response was highly satisfactory and dose-dependent. A remarkable immune response was obtained even with a trace amount of HBsAg. This study further supports recent indication that booster hepatitis B vaccine doses may be unnecessary in healthy adult responders to a full course of hepatitis B vaccination.

Respuesta serológica a una vacuna DNA recombinante en nativos residentes de dos áreas hiperendémicas a hepatitis B en la amazonía peruana / Serogical response to DNA recombinant vaccine in natives living in two different HBV hiperendemic areas of the peruvian amazon jungle

En ámplias zonas de la Selva Amazónica de Brazil, Colombia, Ecuador, Venezuela y Perú se han reportado numerosos focos hiperendémicos de Hepatitis B y Delta. En las tribus del Nor-Oriente peruano (Jívaroes) la prevalencia llegó hasta el 94 por ciento de marcadores HBV, vs el grupo tribal del sur (Arawaka):65.1 por ciento. En éste trabajo hemos estudiado la respuesta vacunal de 226 voluntarios de 6 comunidades Jívaroes y tres Arawaka, suceptibles a ser vacunados con una vacuna DNA recombinante (ENGERIX B). Todos fueron Ag/Ab negativos, aunque el 55.5 por ciento de ellos fueron HBc-Ab positivo. Resultados: el 84.9 por ciento de los nativos seroconvirtió a anti-HBs-Ab y el 73.5 por ciento alcanzó títulos de seroprotección (Mayor de 10 mUI/ml). Mejor respuesta se observó en aquellos que eran core negativo, especialmente en los provenientes de áreas de menor endemicidad (Sur). También observamos buena respuesta a pesar de que hubo que variar el esquema original 0.1.6 meses, pero cuando se prolongó éste a 0,4,14 y 0,4,9 la respuesta decreció a 51.8 por ciento de seroinmunidad. Hubo mejor título protectivo anti HBs en el grupo Sur: 416.3 mUI/ml, comparado con los del Norte, 182.3 mUI/ml.Conclusiones: a) Es importante, en zonas hiperendémica, estudiar previamente marcadores HBV especialmente en adultos. b) El esquema vacunal puede ser modificado básicamente en la tercera dosis hasta por 14 meses; es importante respetar éste en el primer y segundo mes. c) Se obtuvo una buena respuesta anti-HBs protectora: el título promedio obtenido fue de 290.9 mUI/ml (10.2-41,000) en el 73.5 por ciento de los vacunados . d) La vacuna soportó bien todas las dificultades de manejo en el campo. No se presentaron reacciones adversas a la vacuna

Prevalencia de anticuerpos anti-hepatitis A en escolares en la década actual / Prevalence of antibodies against hepatitis A virus in chilean school age children

Background: As sanitary conditions of a population improve, hepatitis A virus infection occurs at higher ages,thus decreasing the prevalence of antibodies against the virus. In the eighties, the prevalence of antibodies among children was 97 percent and depended on the socioeconomic level. Aim: To assess the prevalence of antibodies against hepatitis A virus in school age children living in Valdivia. Subjects and methods: Two thousand three hundred thirty three school age children were studied. Total antibodies against hepatitis A virus were detected using an ELISA kit from Abbott. Children were stratified in age groups and school were classified as private, subsidized, municipal or foster homes. Results: Antibodies were positive in 65 percent of children (59 percent in children aged 6 to 8 years old, 66 percent in children aged 9 to 11 years and 69 percent in children aged 12 to 15 years. In private schools, the prevalence was 26 percent, in subsidized schools the figure was 54 percent, in municipal schools 73 percent and in foster homes 91 percent. Conclusions: The general prevalence of antibodies against hepatitis A virus is higher in low socioeconomic level children. There is a global decrease in the prevalence of these antibodies in the last years