Non-carrier nanoparticles adjuvant modular protein vaccine in a particle-dependent manner.

Nanoparticles are increasingly used to adjuvant vaccine formulations due to their biocompatibility, ease of manufacture and the opportunity to tailor their size, shape, and physicochemical properties. The efficacy of similarly-sized silica (Si-OH), poly (D,L-lactic-co-glycolic acid) (PLGA) and poly caprolactone (PCL) nanoparticles (nps) to adjuvant recombinant capsomere presenting antigenic M2e modular peptide from Influenza A virus (CapM2e) was investigated in vivo. Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the immunogenicity of modular capsomeres, even though CapM2e was not actively attached to the nanoparticles prior to injection (i.e., formulation was by simple mixing). In contrast, PCL nps showed no significant adjuvant effect using this simple-mixing approach. The immune response induced by CapM2e alone or formulated with nps was antibody-biased with very high antigen-specific antibody titer and less than 20 cells per million splenocytes secreting interferon gamma. Modification of silica nanoparticle surface properties through amine functionalization and pegylation did not lead to significant changes in immune response. This study confirms that simple mixing-based formulation can lead to effective adjuvanting of antigenic protein, though with antibody titer dependent on nanoparticle physicochemical properties.

Predicting acute viral hepatitis serum markers (A and E) in patients with suspected acute viral hepatitis attending primary health care centers in Baghdad: a one year cross-sectional study.

BACKGROUND: Viral hepatitis is an important preventable infectious disease with various rates of occurrence in different areas of the world. The main objective of the present study was to evaluate the role of some risk factors in predicting a positive acute viral hepatitis marker among patients with suspected acute viral hepatitis in a primary health care setting in Baghdad. Besides, finding out the occurrence of jaundice, contribution of viruses A and E to the cases that have occurred in Baghdad province was also searched for. METHODS: Over a period of 1 year a descriptive cross sectional study was carried out at the primary health care centers in Baghdad. A questionnaire form was used to collect data about demographic factors and the results of the investigations. Total serum bilirubin and bilirubin in urine were done at the primary health care center laboratory. The rest of the sera samples were sent to Hepatitis referral Lab at Central Public Health Laboratory (CPHL) to be tested for anti HAV IgM and anti HEV IgM using ELISA technique. RESULTS: A total of 7,576,372 consultations to primary health care centers were recorded in Baghdad. Among those a total of 2,692 cases (35.5 per 100,000 consultations) were labeled as acute viral hepatitis cases. A positive hepatitis viral marker (A, B, C and E) was found in 1,332 cases (17.6 per 100,000 consultations). More than two fifths (44.8%) of cases were positive for anti-HAV antibodies and another 1.6% had positive anti-HEV antibodies. CONCLUSION: During 1 year period, the rate of occurrence of suspected acute viral hepatitis cases was 35.5 per 100000 of consultations to the primary health care centers in Baghdad. Of the total suspected cases, only 17.6 per 100000 of the consultations were positive for one of the viral hepatitis markers. Those who tested positive for one of the viral hepatitis markers represent 49.5% of the suspected cases. Proportion of anti HAV IgM positive tests among suspected cases was 44.8%. Factors that were able to predict positive Anti HAV IgM were (younger age group, negative history of cupping or tattooing, negative past history of jaundice). Male gender was the least important predictor of a positive case for anti HAV IgM. Proportion of Anti HEV IgM positive tests among suspected cases was 1.6%. Of the factors studied, only age was able to predict a positive Anti HEV IgM in those more than 15 years. Further studies are recommended.

[Immunological safety and sensitizing effect of an MB-7-based vaccine against hepatitis A]. / Immunologicheskaia bezopasnost' i sensibiliziruiushchee deistvie vaktsiny protiv gepatita A na osnove shtamma MB-7.

The influence of a vaccine based on the MB-7 strain of hepatitis A virus (VP-MB-7) designed at the "Vector" Center of Virology and Biotechnology was studied. VP-MB-7 was found to provoke no allergic response and to have an activating effect on the specific and non-specific responses of cell and humoral immunity similar to those evoked by hepatitis A vaccine "Hep-A-in Vac".

An outbreak of hepatitis A associated with green onions.

Forty-three cases of serologically confirmed hepatitis A occurred among individuals who ate at restaurant A in Ohio in 1998. Serum samples from all restaurant A employees who worked during the exposure period were negative for IgM antibodies to hepatitis A virus (HAV). A matched case-control study determined that foods containing green onions, which were eaten by 38 (95%) of 40 case patients compared with 30 (50%) of 60 control subjects, were associated with illness (matched odds ratio, 12.7; 95% confidence interval, 2.6-60.8). Genetic sequences of viral isolates from 14 case patients were identical to each other and to those of viral isolates from 3 patients with cases of hepatitis A acquired in Mexico. Although the implicated green onions, which could have come from one of 2 Mexican farms or from a Californian farm, were widely distributed, no additional green onion-associated cases were detected. More sensitive methods are needed to detect foodborne hepatitis A. A better understanding of how HAV might contaminate raw produce would aid in developing prevention strategies.

Anti-hepatitis A virus antibody response elicited in mice by different forms of a synthetic VP1 peptide.

Peptide VP1 (11-25) of the capsid of hepatitis A virus was synthesized by the Fmoc-polyamide solid phase method, and administered to mice in different forms: (1) free, (2) encapsulated in multilamellar liposomes, (3) coupled to keyhole limpet hemocyanin (KHL), and (4) incorporated into a tetrameric branched lysine core. The highest anti-VP1 peptide responses were generated by synthetic peptides entrapped into liposomes and coupled to KLH. No anti-HAV response was generated with the free peptide, while all the other forms induced both anti-HAV and HAV-neutralizing antibodies. Maximum neutralization indices were observed in ascites from mice treated with liposome-entrapped and KLH peptides.

Preparation and immunogenicity of an inactivated hepatitis A vaccine.

A hepatitis A vaccine was prepared by formaldehyde inactivation of purified hepatitis A virus (HAV) LSH/S strain grown on human diploid MRC-5 cells. The vaccine was devoid of residual infectivity in vitro and failed to induce in marmoset monkeys any pathological features or variations of haematological and clinical chemistry values. Infectious HAV particles were not detected in faeces and sera of the vaccinated primates by ELISA or after passages in MRC-5 cells. The immunogenicity of the vaccine was evaluated by injecting guinea-pigs with 0.8, 0.2 or 0.05 micrograms of HAV antigen adsorbed onto 0.5 and 1 mg of Al (OH)3 or 0.3 mg of AlPO4. The antibody response, measured by a competitive radioimmunoassay, was dose- and adjuvant-dependent. One injection of 0.2 micrograms of AlPO4-adsorbed HAV antigen induced seroconversion in 100% of animals and high levels of specific and neutralizing serum antibodies. A further increase of antibody titres was observed after the second and third inoculations. These results show that this vaccine formulation is safe and immunogenic in animal models, and suggest that it should be evaluated further by human clinical studies.

Reactogenicity and immunogenicity of inactivated hepatitis A vaccines.

Two inactivated hepatitis A virus (HAV) candidate vaccine strain were tested, derived from strains CLF and HM175. Neither vaccine increased liver enzymes levels and reactogenicity was similar to that observed with other alum-absorbed products. Antibody responses were dose-dependent and protection against HAV can be presumed to last for at least three years. All persons receiving 720 ELISA units (El.U) of the CLF vaccine seroconverted after one dose. For the HM175 vaccine, anti-HAV persisted until month 12 after injections at months 0 and 1, suggesting that the third dose of vaccine could be given at any time from month 6 to 12. A double dose of HM175 vaccine (1440 El.U) given as a single bolus resulted in 100% seroconversion by day 14 with a geometric mean anti-HAV level of 121 mIU/ml. This implies that rapid protection can be induced using large doses of inactivated HAV vaccine should time constraints dictate such an approach.