Dietary plant stanol ester consumption improves immune function in asthma patients: results of a randomized, double-blind clinical trial.

BACKGROUND: In vitro and ex vivo studies have suggested that plant sterols and stanols can shift the T helper (Th) 1/Th2 balance toward a Th1-type immune response, which may be beneficial in Th2-dominant conditions such as asthma and allergies. OBJECTIVE: We evaluated in vivo whether plant stanol esters affect the immune response in asthma patients. DESIGN: Fifty-eight asthma patients participated in a randomized, double-blind, placebo-controlled intervention study. All subjects started with a 2-wk run-in period in which they consumed 150 mL control soy-based yogurt without added plant stanol esters/d. Next, an 8-wk experimental period was started in which one-half of the participants received plant stanol enriched soy-based yogurts (4.0 g plant stanols/d), whereas the other one-half of subjects continued the consumption of control yogurts. After 4 wk of daily plant stanol consumption, all participants were vaccinated against hepatitis A virus (HAV), and the increase of antibody titres was monitored weekly until 4 wk after vaccination. RESULTS: Asthma patients in the plant stanol ester group showed higher antibody titres against HAV 3 and 4 wk after vaccination [19% (P = 0.037) and 22% (P = 0.030), respectively]. Also, substantial reductions in plasma total immunoglobulin E, interleukin (IL)-1ß, and tumor necrosis factor-α were shown in the plant stanol ester group. The increase in serum plant stanol concentrations was correlated significantly with the decrease in IL-13 concentrations and the Th1 switch in the Th1/Th2 balance. However, no absolute differences in cytokine production between the plant stanol ester group and the control group were shown. CONCLUSION: To the best of our knowledge, we are among the first authors to show that plant stanol ester consumption improves the immune function in vivo in asthma patients. This trial was registered at clinicaltrials.gov as NCT01715675.

Combined hepatitis A and B vaccine: providing a bright future for preventing hepatitis.

The first combined hepatitis A and B vaccine has been available in the United States since 2001. The vaccine provides protection against viral hepatitis with rapid seroprotection and lasting immunogenicity. This review outlines the product's components, clinical efficacy and opportunities for use in special circumstances. The vaccine has a good safety profile and has good tolerability. The combined hepatitis A and B vaccine is a well studied vaccine that provides rapid seroconversion with a good safety profile.

Functional recombinant human anti-HAV antibody expressed in milk of transgenic mice.

Hepatitis A virus (HAV) is a wide spread pathogenic agent and is the common cause of acute Hepatitis A worldwide. Passive immunization of HAV plays an extremely important role in post-exposure prophylaxis with clinical applications often requiring large amounts of antibody. As an alternative to the in vitro production of recombinant proteins, expression of monoclonal antibodies (mAbs) in the milk of transgenic animals is currently used being associated with low production costs and high activity. In this paper, eight founder lines of transgenic mice were generated by co-microinjection of the two cassettes encoding the heavy- and light-chains of a neutralizing anti-HAV antibody, respectively. The expressed heavy- and light-chains of the mAb were correctly assembled and modified in the mammary gland as detected by western blotting. High expression levels of the antibody were achieved during the lactation period and found to be independent of the copy numbers of integrated transgenes. The highest level was up to 32.2 mg/ml. The binding specificity and neutralizing activity of the expressed mAb were assayed by ELISA and neutralizing test, showing that it is capable to neutralize the JN strain of Hepatitis A virus efficiently. Therefore, our results suggest that a large-scale and efficient production of the anti-HAV mAb in the milk of transgenic farm animals would be feasible in the future.

[Efficacy of vaccination against hepatitis A in HIV infected adults from Lodz region--preliminary report]. / Ocena skutecznosci szczepienia przeciwko wirusowemu zapaleniu watroby typu A w grupie doroslych osób zakazonych HIV z regionu lódzkiego--doniesienie wstepne.

OBJECTIVE: To estimate the prevalence of anti-HAV-T in the group of HIV-positive adults and to assess the efficacy of vaccination against viral hepatitis A. MATERIAL AND METHODS: In HIV-infected outpatients anti-HAV-T was determined (electrochemiluminescence method). Patients susceptible to HAV infection were qualified for vaccination. RESULTS: In the group of 175 HIV-infected patients, 70 persons (40%) were anti-HAV-T positive. Prevalence of anti-HAV-T was significantly higher in patients over 35 years of age. Anti-HAV-T were present in all individuals older than 50 years. So far 47 patients have completed vaccination. Good response (detectable anti-HAV-T 1 month after booster dose) was obtained in 73,0% patients. Individuals with actual CD4 count above 200 cells/ul responded better (81,2%) than persons with CD4 count 200 cells/ul or lower (20%). Nadir CD4 count above 50 cells/ul predicted better response than 50 cells/ul or below (78,8% and 25% respectively). One year after vaccination anti-HAV-T were still detectable in 21 patients (56,8%). CONCLUSIONS: 1. Most of studied HIV-positive patients (60%) were susceptible to HAV infection and should be vaccinated. 2. Good response to vaccination was obtained in 73% of patients and it was higher in persons with actual CD4 count above 200 cells/ul and nadir CD4 count above 50 cells/ul.

Recent advances with a virosomal hepatitis A vaccine.

BACKGROUND: Epaxal, a virosomal vaccine against hepatitis A virus (HAV) infection, has been in use for nearly 15 years, especially among at-risk adults. Recent studies have shown that it is also a potent vaccine for children. OBJECTIVE: To summarise recent advances of Epaxal Junior (0.25 ml, paediatric formulation). METHODS: Published papers reporting results on the virosomal HAV vaccine were abstracted and reviewed. RESULTS/CONCLUSION: In a comparative randomised trial, the paediatric dose was found to be highly immunogenic and non-inferior to the standard dose with respect to seroprotection rates. The concomitant administration of virosomal HAV vaccine with routine childhood vaccines was investigated in another trial. The virosomal HAV vaccine did not interact with the antibody response of routine childhood vaccines which in turn did not reduce the antibody response to HAV. In countries that recommend immunisation against hepatitis A, this virosomal vaccine is an excellent candidate with few side effects at the site of injection.

Preliminary evidence that morning vaccination is associated with an enhanced antibody response in men.

Variation in response to vaccination, particularly in vulnerable groups, provides a strong rationale for developing vaccine adjuvants. If there were consistent diurnal variation in immune response, this could inform a simple intervention for enhancing vaccine efficacy. Data from two studies are presented examining morning versus afternoon vaccine administration; in the first, hepatitis A vaccine was administered to young adults, and in the second, influenza vaccine to older community-based adults. Men, but not women, vaccinated in the morning mounted a better peak antibody response to both hepatitis A and the A/Panama influenza strain. These results indicate that it would be worthwhile testing this effect in a large randomized control trial with vaccination during time periods representing the extremes of hormonal and cytokine diurnal rhythms.

Long-term immunogenicity after single and booster dose of a live attenuated hepatitis A vaccine: results from 8-year follow-up.

Live, attenuated hepatitis A vaccines are used widely in China but there is uncertainty regarding the persistence of vaccine-induced anti-HAV antibodies after single dose and booster dose administrated at month 12. A large scale clinical trial to evaluate the live, attenuated hepatitis A vaccine was conducted in Hebei province between 1996 and 1999. Five years after the trials, children in single dose and booster dose groups were bled and followed. Seventy two percent (61/85) of children who received a single trial dose had detectable anti-HAV antibodies for 96 months (GMC at 96 months: 89.0 mIU/mL). In the booster group 98% (48/49) children remained anti-HAV positive with GMC of 262.8 mIU/mL at month 96. The reinjection with live attenuated HAV vaccine can elicit a booster effect. Results from single dose group seems not to support the need for booster doses of live attenuated hepatitis A vaccine in immunocompetent individuals regarding the persisting anti-HAV and anamnestic response of a single dose vaccine. Continued monitoring of anti-HAV antibodies is needed for a rational hepatitis A immunization strategy in China.

Antibody persistence and immune memory elicited by combined hepatitis A and B vaccination in older adults.

Response to hepatitis A and B vaccines has been reported to decline with age. This open, prospective, single-site study examined the long-term response to the combined hepatitis A/B vaccine Twinrix in 98 primary responders aged 45-67 years. Levels of antibody against hepatitis A virus (HAV) and hepatitis B surface antigen (HBs) were tested 30 months after initial vaccination. At this stage, all participants remained seropositive for anti-HAV and 70% for anti-HBs. A booster vaccination was offered to those who had responded to the first vaccination but then lost protective levels of anti-HBs. An anamnestic response was observed in all cases.

Immunogenicity of hepatitis a vaccine in children with cancer.

This study evaluated the immuned response of the hepatitis A vaccine in children with cancer who were receiving chemotherapy. Twenty-eight patients with lymphomas or solid tumors and who had negative serology for hepatitis A were enrolled. The median age was 4.7 years (range 2-16). The patients received 1440 IU hepatitis A vaccine at 0 and 6 months. Seroconversion rates at the first and seventh months were 60% (n = 17/28 patients) and 89% (n = 24/27 patients). No adverse effects were observed. The hepatitis A vaccine was found to be effective and safe in children with cancer.

Long-term immunity in young adults after a single dose of inactivated Hepatitis A vaccines.

We evaluated in a prospective study the immune response of naïve subjects to a single dose of inactivated Hepatitis A vaccine. Ninety-seven percent of the vaccinees sero-converted 1 month after vaccination and 93% were still positive 2 years later. All of the vaccinees had a strong booster response 2 years after the single dose. Avaxim was more immunogenic than Vaqta for the primary dose (p = 0.01 for sero-positivity, p<0.001 for antibody level) but no differences were found after boosting with Avaxim. Performance of intense physical activity during the first month after a single vaccine dose was associated with lower antibody levels (p = 0.004). This study indicates that a single dose of inactivated HAV vaccine elicits protective immune memory for at least 2 years.

Response to hepatitis A vaccine in HIV patients in the HAART era.

We evaluated the development of hepatitis A antibody after vaccination in a large cohort of patients studied in a clinical setting after the introduction of HAART. Overall, 130 of 214 vaccinated individuals developed hepatitis A antibody. In a multivariate analysis, only the CD4 cell count at the time of vaccination was associated with an absence of response. The lack of association with the nadir CD4 cell count suggests that patients will respond to vaccine after immunological reconstitution in response to HAART.

Immunogenicity and tolerability of hepatitis A vaccine in HIV-infected children.

The immunogenicity and tolerability of hepatitis A virus vaccine was evaluated in a group of 32 children with human immunodeficiency virus (HIV) infection and 27 children with seroreversion. After 2 doses of vaccine, 100% of children experienced seroconversion with good toleration of the vaccine. There were no differences in variation of virus load between immunized HIV-positive children and a group of 31 nonimmunized HIV-positive children with similar characteristics.

Immunogenicity, reactogenicity and adherence to a combined hepatitis A and B vaccine in illicit drug users.

AIMS: The use of illegal drugs is associated with an increase in infective risk for the hepatitis viruses, against which the vaccination of drug users (DUs) is recommended unanimously. The aim of the study was to determine tolerability, adherence and immune response of a combined vaccine providing dual protection against hepatitis A virus (HAV) and hepatitis B virus (HBV). METHODS: The vaccine was administered to 38 DU, attending three public health centres for drug users in northern Italy, with a three-dose schedule (at 0, 1 and 6 months). The vaccine was well tolerated: only one adverse reaction (fever) was recorded after the 110 doses administered (0.9%). The vaccine schedule was completed successfully in 35 cases (92.1%). At month 8, in 34 subjects (89.5%) antibody response was evaluated: all showed seroprotection for HAV and in 33 subjects (97.1%) for HBV. CONCLUSIONS: The vaccine, studied for the first time in DUs, proved to be safe, well accepted and immunogenic; anti-HAV response was 1272 mIU/ml and 1726 mIU/ml for anti-HBV, titres lower than reported in literature for the general population. This study suggests that DUs who are HAV/HBV-negative could be vaccinated with combined vaccine.

Immunogenicity of booster vaccination with a virosomal hepatitis A vaccine after primary immunization with an aluminum-adsorbed hepatitis A vaccine.

BACKGROUND: Increasing numbers of individuals are traveling to areas of high hepatitis A endemicity and require immunization against the hepatitis A virus (HAV). The option of using a virosomal, aluminum-free, HAV vaccine (Epaxal) for booster immunization following primary vaccination with an aluminum-adsorbed vaccine has been assessed. METHODS: In total, 142 healthy subjects, 79 men and 63 women, aged 12 to 72 years, were injected intramuscularly with a booster dose of Epaxal (0.5 mL containing < or =500 RIA units of HAV antigen) 6 to 24 months after primary vaccination with Havrix (0.5 or 1.0 mL containing 720 or 1440 ELISA units of HAV antigen, respectively, adsorbed onto aluminum hydroxide). Anti-HAV antibody titers were measured on days 0 and 28 by an enzyme immunoassay. Adverse events were recorded for 1 month postinjection. RESULTS: Overall, 98/118 subjects (83%) with no serologic evidence of past HAV infection were still seroprotected at enrolment (anti-HAV antibody titer < or = 20 mIU/mL). The seroprotection rate was 87% in those primed with Havrix 1440 6 to 12 months earlier (n=93) and 60% in those primed < or =12 months before enrolment (n=20, mean 16 months). The geometric mean anti-HAV antibody titer increased from 65 mIU/mL at day 0 to 1,722 mIU/mL at day 28 after a single booster dose with Epaxal in evaluable subjects who were primarily vaccinated with either a single dose of Havrix 1440 (n=111) or two separate doses of Havrix 720 (n=4). All subjects were seroprotected at day 28, and 98% showed at least a four-fold increase in anti-HAV antibody titer. Epaxal was well tolerated and no serious adverse events were reported. At day 28, the tolerability of the vaccination was judged as either "very good" or "good" by 96% of vaccinees and by all investigators. CONCLUSION: Epaxal can be successfully used to boost immunization following primary vaccination with an aluminum-adsorbed vaccine, and is well tolerated.

[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".

Immune responses of anti-HAV in children vaccinated with live attenuated and inactivated hepatitis A vaccines.

The immunogenicity of a live attenuated HAV vaccine and an inactivated HAV vaccine was compared. Altogether 117 children were vaccinated with either the inactivated or the live attenuated vaccine. Children were bled at months 1, 6, 7, 12 and 24, and the anti-HAV total IgG antibody and IgG subclass profile were assessed. In both vaccinated groups, the geometric mean titer (GMT) of anti-HAV peaked 7 months after the initial dose and declined during the following months. The IgG subclass profiles in both vaccinated groups were highly restricted to IgG1 and IgG3. Both vaccines have been shown highly effective in preventing viral hepatitis A in former studies.

Purification and characterization of recombinant human anti-HAV monoclonal antibody.

In order to obviate the drawbacks of plasma immunoglobulins, the whole molecular recombinant human anti-HAV (hepatitis A virus) monoclonal antibody (anti-HAV IgG) produced and secreted by rCHO cells was purified and its physicochemical properties were extensively characterized. The rCHO cells were cultured in serum-free medium and the supernatants were collected. The recombinant human IgG molecules were sequentially purified by ultrafiltration, rProtein A Sepharose Fast Flow affinity chromatography, ion exchange chromatography and diafiltration. In affinity chromatography, prior to the target protein elution, an intermediate high salt wash step was inserted, different pH and salt concentrations were evaluated for the capacity of removing host cell DNA. The yield of the downstream purification process was approximately 40%. The purity of anti-HAV IgG thus generated was assayed with SEC-HPLC method, integration result showed that the monomeric IgG content was more than 99%. Western-blot was carried out with AP-antiHuman IgG (Fab specific) and AP-antiHuman IgG (Fc specific) respectively, the blot result demonstrated that the anti-HAV IgG is human antibody with Fab and Fc structure. The specific anti-HAV activity determined by ELISA was 100 IU/mg, with anti-HAV immunoglobulin as the working standard reference. Ligand leakage in the eluate of the affinity column was approximately 32 ng/mg IgG, while after further purification steps, it was decreased to less than 2 ng/mg IgG. Residual host cell DNA was monitored with solid dot blot assay, DNA can be removed effectively with intermediate high salt wash step in the affinity chromatography. Free sulfhydryl content of anti-HAV IgG was assayed with fluorescent spectrophotometer, the low molecular weight bands appeared in non-reducing SDS-PAGE may be caused by the presence of free sulfhydryl. The endotoxin content was less than 1EU/ mg examined by standard LAL test procedures. Anti-HAV IgG prepared with this process is able to fulfill the regulatory requirements of State Food and Drug Administration for recombinant products.

Persistence of immunity and seroprotection 4 years after a primary vaccination schedule with a Hansenula polymorpha recombinant hepatitis B vaccine.

To evaluate the persistence of the immune response in a population of healthy volunteers that had been vaccinated with a new Hansenula polymorpha recombinant hepatitis B vaccine in a previous clinical study 4 years before, we measured the titre of anti-HBs. All, but one of the evaluated volunteers remained protected. None of them had experienced any adverse event related to the vaccine from the moment of immunization, to the present. The vaccine proved to be immunogenic and to confer long-term protection in this group.

Sleep enhances the human antibody response to hepatitis A vaccination.

OBJECTIVE: The common belief that sleep supports immune defense has received surprisingly little direct experimental support. The antibody response to vaccination provides a valid tool to assess the influence of sleep on adaptive immune functioning in humans, which is also clinically relevant. METHODS: Two groups of healthy humans (N = 19) not previously infected with hepatitis A virus (HAV) were studied. On the night after primary vaccination with inactivated HAV, which took place at 0900 hours, one group had regular sleep. The other group stayed awake, and did not sleep before 2100 hours the following day. HAV antibody titers were measured repeatedly until 28 days after vaccination. Plasma hormone concentrations and white blood cell (WBC) subset counts were determined on the night and day after vaccination. RESULTS: Subjects who had regular sleep after vaccination, displayed a nearly two-fold higher HAV antibody titer after 4 weeks than subjects staying awake on this night (p=.018). Compared with wakefulness, sleep after vaccination distinctly increased release of several immune-stimulating hormones including growth hormone, prolactin, and dopamine (p <.01). Concentrations of thyrotropin, norepinephrine, and epinephrine were lowered by sleep (p <.02), whereas sleep only marginally influenced WBC subset counts. CONCLUSIONS: Data suggest that sleep compared with sleep deprivation on the night after vaccination improves the formation of antigen-specific immune defense as reflected by antibody production in humans. Sleep presumably acts by inducing a hormonal environment in secondary lymphoid tissues, enhancing lymphocyte proliferation and differentiation and finally antibody synthesis. Results underscore the importance of sleep for immunocompetence.