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Administration of combined diphtheria and tetanus toxoids and pertussis vaccine, hepatitis B vaccine, and Haemophilus influenzae type b (Hib) vaccine to infants and response to a booster dose of Hib conjugate vaccine.

We compared antibody levels following separate but simultaneous administration of diphtheria and tetanus toxoids with acellular pertussis vaccine (DTaP) containing pertussis toxoid, filamentous hemagglutinin, and pertactin (PRN); hepatitis B vaccine; and Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate; PRP) vaccine conjugated to tetanus toxoid (PRP-T) with those following administration of a combination of a DTaP-hepatitis B vaccine-PRP-T to infants at 2, 4, and 6 months of age. The antibody response to a booster dose of PRP conjugate vaccine (CRM197-OS) in infants with low (< 1 microgram/mL) or undetectable (< 0.10 microgram/mL) postpriming levels of antibody to PRP was also studied. Antibody levels were quantitated before and after dose 3 by enzyme-linked immunosorbent assay, radioimmunoassay, or neutralization assay. Seroresponse rates were not different between the two vaccine groups except for rates of response to PRP. There was a trend that levels of antibody to all the antigens included in the combination vaccine were lower than those of antibody to antigens in separate vaccines; for levels of antibody to diphtheria toxoid (P = .001), PRN (P < .0001), and PRP (P < .0001), the differences were significant. Despite low or undetectable postpriming levels of antibody to PRP, high-titered (geometric mean concentration, 9.02 micrograms/mL; range, 1.0-81.5 micrograms/mL), immunoglobulin G-predominant antibody to PRP was produced following a booster dose of CRM197-OS, a finding consistent with a memory response.

Diphtheria-Tetanus-Pertussis Vaccine↗

Hepatitis vaccines.

Viral hepatitis accounts for substantial morbidity and mortality worldwide, To date, the molecular sequences of six hepatotropic viruses have been described and designated hepatitis A, B, C, D, E, and G. Various methods have been employed to decrease the occurrence of these diseases, and advances in vaccination strategies have aided in prevention of viral hepatitis. There are currently two FDA-approved vaccines licensed for use in the United States, aimed at eradication of hepatitis A and hepatitis B viral infection. A considerable amount of research has been devoted to the development of these vaccines, and progress has been made toward the development of vaccines aimed at the other hepatotropic viruses. In this article, the development and current status of the vaccines directed against the hepatitis viruses are reviewed.

Flaviviridae↗

Thymopentin administration and increase of sero-conversion after B-hepatitis vaccine in diabetic patients.

We have previously reported that 40% of diabetic patients have an impaired specific immune response after vaccination against B-hepatitis. Thymopentin (TP5), the active site of thymopoietin hormone, has been shown to increase antibody response (HbsAb) following B-hepatitis vaccination in several disease conditions. In the present study TP5 (50 mg) was administered subcutaneously three times per week to 17 diabetic patients for a week prior B-hepatitis vaccination and for three weeks afterwards. Sero-conversion was observed after the third dose of vaccine in 15 out of 17 (88%) patients and in 94% of a group of normal subjects acting as control. Although the median HbsAb titre was significantly lower in diabetics compared to normal subjects, we conclude that administration of TP5 in diabetic patients increases the rate of sero-conversion following B-hepatitis vaccination.

Adjuvants, Immunologic↗

Hepatitis vaccination among drug users.

Hepatitis virus infections are traditionally a major health problem among drug users (DUs). Several factors may favor the rapid spread of hepatitis infection in this category of patients. HBV and HCV are easily transmitted through exposure to infected blood and body fluids. DUs often prepare and use drug solutions together. Many in the DU community are infected and this provides multiple opportunities for transmission to others. Many of these patients with chronic hepatitis virus infection are not aware of their infections and this facilitates the spread of the diseases. Viral hepatitis is not inevitable for DUs. Although multiple factors have prevented the development of vaccines for hepatitis C, both hepatitis A and hepatitis B can be prevented by immunization. The purpose of this overview is to summarize and discuss the hepatitis vaccination in this population.

Hepatitis A↗

Release potency tests of hepatitis vaccines.

SmithKline Beecham Biologicals produces two vaccines against hepatitis: hepatitis B (Engerix-B) introduced in 1986 and hepatitis A (Havrix) introduced in 1991. Using these two examples, we demonstrate the long and gradual transition process towards an in vitro release test for potency and a significant decrease in the number of animals needed for vaccine release.

Animal Testing Alternatives↗

Hepatitis vaccines.

The 1980s represented a decade of breakthroughs for the development of hepatitis vaccines. Plasma-derived and then recombinant hepatitis B vaccines were developed and introduced, killed hepatitis A vaccine was developed, and the virologic tools were discovered with which to lay the groundwork for a vaccine against hepatitis C. Even as the focus of the 1990s shifts toward antiviral therapy of chronic viral hepatitis, we cannot afford to neglect the importance of prevention by vaccination. Better vaccines and improved vaccination strategies for preventing hepatitis A and B will continue to demand research investment, and the most meager toehold will have to be exploited and pursued aggressively if a practical, effective hepatitis C vaccine is to be developed.

Adolescent↗

Perspectives on hepatitis B infections and the efficacy of vaccination (hepatitis B and pneumococci) in dialysis patients.

Hepatitis B is a well known problem in dialysis units. We therefore examined the historical frequency of hepatitis B carriers in our unit, our vaccination program to hepatitis B virus (HBV), the response to hepatitis B vaccine, the IgG subclass response of anti-HBs and the response and IgG subclass response to pneumococcal vaccination (another vaccine) in dialysis patients. From 1970 and onwards 23 HBV carriers were found, but no new cases of hepatitis B occurred during the study period, i.e. from 1980 and onwards. Only one of the carriers was alive by the end of 2001. In four patients liver disease (in one of them liver cirrhosis) may have been a concomitant cause of death. The antibody response to hepatitis B vaccine was significantly lower in patients than in staff. In four patients a fourth injection was cancelled due to transplantation and bad health, while such data were lacking in 8 cases. In anti-HBs positive patients and controls a significant difference in the response of healthy adults was observed in anti-HBs IgG1 (p < 0.001) vs all other IgG subclasses. Dialysis patients had low levels, or negative findings, in all cases, with IgG1 as the highest proportion found (3/11 patients). An antibody response to pneumococcal vaccination was registered in 25 out of 29 dialysis patients (in all 86%). The IgG-subclass vaccination response to pneumococci in 28 dialysis patients was mainly IgG2 and IgG1 but also occurred in IgG3 and IgG4. Prevaccination antibody levels of the controls were higher in IgG1 and IgG2 (p < 0.01) (n = 21) than in dialysis patients (n = 28). Hepatitis B is nowadays a rare, but still dangerous disease in nephrology units. Dialysis patients have a reduced response to hepatitis B vaccine and vaccination schedules should be started early as some patients otherwise may not receive a fourth injection. The adequate antibody response to pneumococcal vaccination mainly due to IgG2 and IgG1 antibodies indicates that the antigen involved is important in vaccination responses in dialysis patients.

Case-Control Studies↗

Hepatitis A, hepatitis B, and combination hepatitis vaccines for immunoprophylaxis: an update.

Since the publication of the last extensive review of hepatitis vaccines, use of inactivated hepatitis A vaccines has been extended to high-risk regions of the United States and specific patient groups, such as those with chronic liver disease, and use of the recombinant hepatitis B vaccines has been recommended for older adolescents. A combination hepatitis A and B vaccine, recently approved for licensure by the US Food and Drug Administration, should increase convenience and compliance, reduce the costs of vaccination, and provide prolonged and dual protection for those at risk for hepatitis. Although commercially available vaccines for hepatitis C, D, and E remain a distant goal, advances in vaccine and adjuvant technology, including immunization with DNA-based vaccines, hold promise for the future.

Adult↗

Hepatitis vaccines: recent advances.

Despite the availability of hepatitis A vaccines that might provide protection for decades, hepatitis B vaccines that provides protection for at least 15 years and the recent introduction of a combined hepatitis A and B vaccine, these infections continue to spread in both the developed and developing world. Hepatitis A vaccine coverage has been limited to high-risk groups: such a selective immunisation policy is unlikely to have a major impact. If adequate immunogenicity in infants is confirmed, dosing schedules can be improved and the costs of vaccination reduced, universal paediatric immunisation with combined hepatitis A and B products is likely to result in the eventual eradication of these infections. In the interim, novel hepatitis A vaccines are being investigated and additional studies on hepatitis A vaccine immunogenicity in infants are in progress. Worldwide use of hepatitis B vaccines for the newborn, young children and high-risk groups should control this infection and obviate the need for a vaccine against hepatitis D. Newer hepatitis B vaccines that may reduce the likelihood of non-responsiveness and have immunotherapeutic value are under study. A recombinant hepatitis E vaccine for use in endemic regions is currently in clinical trials. The development of an effective hepatitis C vaccine has been agonisingly slow and many impediments have been recognised. These include the lack of a susceptible small animal, a high degree of hepatitis C virus (HCV) genomic diversity and failure to produce high quantities of HCV in tissue culture. The development of a novel HCV replicon system may be a major breakthrough. Nonetheless, it may still be exceedingly difficult to produce a vaccine that uniformly provides sterilising immunity; the possibility of developing a hepatitis C vaccine that can prevent chronic infection is an exciting concept that requires further investigation. Advances in recombinant technology, the use of novel genetic (DNA-based) vaccines, expression of hepatitis antigens in plants and improved adjuvants also hold considerable promise.

Genome↗

Hepatitis B exposure and the emergency physician: risk assessment and hepatitis vaccine update.

Since the hepatitis B vaccine was licensed in 1981, emergency physicians have had the opportunity to be immunized against the hepatitis B virus (HBV). The factors that affect the decision to undergo vaccination include the risk of acquiring an HBV infection in emergency practice, the prevaccination immune status of emergency physicians who have knowledge of their hepatitis serum marker profile, and the efficacy and safety of the vaccine. Emergency physicians have a significant risk of acquiring an HBV infection and are recommended by the Centers for Disease Control to receive vaccination. However, emergency physicians are often incidentally tested for HBV serum markers before immunization. Recent investigations have shown that seropositivity for hepatitis surface antibody (anti-HBs) does not necessarily preclude the need for immunization. Finally, experience with 750,000 doses has shown that it is a highly effective and extremely safe vaccine.

Emergency Medicine↗

Cost-effectiveness of hepatitis A/B vaccine versus hepatitis B vaccine in public sexually transmitted disease clinics.

BACKGROUND: Many patients seen at U.S. sexually transmitted disease (STD) clinics are offered hepatitis B vaccination. Substituting hepatitis A/B vaccine would provide additional protection but increase costs. GOAL: The goal was to estimate the cost effectiveness of hepatitis A/B versus B vaccination for 1,000,000 public STD clinic attenders. STUDY DESIGN: A Markov model of hepatitis A outcomes was developed using published literature, U.S. government databases, and expert panel opinion. Added vaccination costs were compared with savings from reduced hepatitis A treatment. Net costs were compared with life-years saved and quality-adjusted life-years (QALYs) gained. RESULTS: Substituting hepatitis A/B vaccine would prevent 2263 overt hepatitis A infections, 292 hospitalizations, 8 premature deaths, and the loss of 281 QALYs. Net health system costs would be $20,892 per life-year saved, or $13,397 per QALY gained. CONCLUSION: Substituting hepatitis A/B for hepatitis B vaccine would reduce morbidity and mortality in a cost-effective manner.

Adolescent↗