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.

[1]  M. Ki,et al.  The changing epidemiology of hepatitis A in children and the consideration of active immunization in Korea. , 2000, Yonsei medical journal.

[2]  M. San-Martín,et al.  Cost analysis of two strategies for hepatitis A vaccination of hospital health-care personnel in an intermediate endemicity area. , 2001, Vaccine.

[3]  S. Iwarson,et al.  Excellent Booster Response 4-6 y after a Single Primary Dose of an Inactivated Hepatitis A Vaccine , 2002, Scandinavian journal of infectious diseases.

[4]  R. Janssen,et al.  Seroprevalence of and risk factors for hepatitis A infection among young homosexual and bisexual men. , 1997, Journal of Infectious Diseases.

[5]  P Van Damme,et al.  Single dose inactivated hepatitis A vaccine: Rationale and clinical assessment of the safety and immunogenicity , 1994, Journal of medical virology.

[6]  A Jakins,et al.  The cost of hepatitis A infections in American adolescents and adults in 1997 , 2000, Hepatology.

[7]  N. Bodsworth,et al.  Response to hepatitis A vaccination in human immunodeficiency virus-infected and -uninfected homosexual men. , 1997, The Journal of infectious diseases.

[8]  H. Margolis,et al.  Effect of postexposure vaccination in a chimpanzee model of hepatitis A virus infection , 1994, Journal of medical virology.

[9]  S. Ellenberg,et al.  Two-year review of hepatitis A vaccine safety: data from the Vaccine Adverse Event Reporting System (VAERS). , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  Man-Fung Yuen,et al.  Viral hepatitis B , 2003, The Lancet.

[11]  D. Vaughn,et al.  Age-specific prevalence of hepatitis A antibody in Thai children. , 1995, The Southeast Asian journal of tropical medicine and public health.

[12]  J. E. Swanson,et al.  Hepatitis A in day-care centers. A community-wide assessment. , 1980, The New England journal of medicine.

[13]  A. Safary,et al.  Clinical experience with an inactivated hepatitis A vaccine. , 1995, The Journal of infectious diseases.

[14]  J. South-Paul,et al.  Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines. , 2000, Vaccine.

[15]  R. Steffen Risk of hepatitis A in travellers. , 1992, Vaccine.

[16]  M. Fabre,et al.  Liver failure in children with hepatitis A , 1997, Hepatology.

[17]  P. Reinke,et al.  RAPID DECLINE OF ANTIBODIES AFTER HEPATITIS A IMMUNIZATION IN LIVER AND RENAL TRANSPLANT RECIPIENTS , 2001, Transplantation.

[18]  M. Just,et al.  Reactogenicity and immunogenicity of inactivated hepatitis A vaccines. , 1992, Vaccine.

[19]  J. Peetermans Production, quality control and characterization of an inactivated hepatitis A vaccine. , 1992, Vaccine.

[20]  P. van Damme,et al.  Cost-effectiveness analysis of hepatitis A prevention in travellers. , 1992, Vaccine.

[21]  E. Keeffe Is hepatitis A more severe in patients with chronic hepatitis B and other chronic liver diseases? , 1995, The American journal of gastroenterology.

[22]  M. Polz-Dacewicz,et al.  Changing epidemiology of hepatitis A virus infection--a comparative study in central eastern Poland (1990-1999). , 2000, Medical science monitor : international medical journal of experimental and clinical research.

[23]  H. Rotman,et al.  Hepatitis A antibody titres after infection and immunization: implications for passive and active immunization , 1993, Journal of medical virology.

[24]  R. Dal-Ré,et al.  Interference assessment of yellow fever vaccine with the immune response to a single-dose inactivated hepatitis A vaccine (1440 EL.U.). A controlled study in adults. , 1996, Vaccine.

[25]  T. Imperiale,et al.  Cost‐effectiveness analysis of hepatitis A vaccination strategies for adults , 1999, Hepatology.

[26]  M. Ciocca Clinical course and consequences of hepatitis A infection. , 2000, Vaccine.

[27]  D. Wilton,et al.  [Hepatitis A]. , 1980, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[28]  J. Löwer,et al.  A new cluster of hepatitis A infection in hemophiliacs traced to a contaminated plasma pool , 1999, Journal of medical virology.

[29]  G. Kanra,et al.  Clinical trial to evaluate immunogenicity and safety of inactivated hepatitis A vaccination starting at 2-month-old children. , 2000, The Turkish journal of pediatrics.

[30]  J. Beran,et al.  Seroprevalence of viral hepatitis A in the Czech Republic , 1999, European Journal of Epidemiology.

[31]  K. Herck,et al.  Long-term persistence of anti-HAV antibodies: model-based calculations of long-term persistence of anti-HAV antibodies after vaccination , 1997 .

[32]  R Prymula,et al.  Concomitant vaccination against hepatitis A and typhoid fever. , 1998, Journal of travel medicine.

[33]  R. Jacobs,et al.  Cost effectiveness of vaccinating food service workers against hepatitis A infection. , 2000, Journal of food protection.

[34]  M. Meltzer,et al.  The economics of vaccinating restaurant workers against hepatitis A. , 2001, Vaccine.

[35]  A. Safary,et al.  Simultaneous passive and active immunization against hepatitis A. , 1992, Vaccine.

[36]  A. Safary,et al.  Efficacy of Hepatitis A Vaccination in Children Aged 12 to 24 Months , 2001 .

[37]  G. De Serres,et al.  Hepatitis A among workers from a waste water treatment plant during a small community outbreak. , 1997, Occupational and environmental medicine.

[38]  P. van Damme,et al.  A single dose, combined vaccine against typhoid fever and hepatitis A: consistency, immunogenicity and reactogenicity. , 2006, Journal of travel medicine.

[39]  B. Bell,et al.  Hepatitis A: how to match prevention strategies to changing epidemiology. , 2000, Vaccine.

[40]  P. Kunasol,et al.  Protection against hepatitis A by an inactivated vaccine. , 1994, JAMA.

[41]  H. Margolis,et al.  The diverse patterns of hepatitis A epidemiology in the United States-implications for vaccination strategies. , 1998, The Journal of infectious diseases.

[42]  M. Shapiro,et al.  Efficacy of an inactivated hepatitis A vaccine in pre- and postexposure conditions in marmosets. , 1995, The Journal of infectious diseases.

[43]  S. Emerson,et al.  Transmission of Hepatitis A to Patients with Hemophilia by Factor VIII Concentrates Treated with Organic Solvent and Detergent To Inactivate Viruses , 1994, Annals of Internal Medicine.

[44]  P. Beutels,et al.  Mathematical models for assessment of long‐term persistence of antibodies after vaccination with two inactivated hepatitis A vaccines , 2000, Journal of medical virology.

[45]  A. Safary,et al.  Immunogenicity and safety in adults of hepatitis A virus vaccine administered as a single dose with a booster 6 months later , 1994, Journal of medical virology.

[46]  Findor,et al.  Response to Hepatitis A Vaccine in Children after a Single Dose with a Booster Administration 6 Months Later. , 1996, Journal of travel medicine.

[47]  C. Chan,et al.  Single dose-inactivated hepatitis A vaccination schedule for susceptible youngsters. , 1996, The American journal of gastroenterology.

[48]  R. Corona,et al.  Travel-associated hepatitis A: effect of place of residence and country visited. , 1991, Journal of public health medicine.

[49]  P. van Damme,et al.  Increased risk for hepatitis A among female day nursery workers in Belgium. , 1994, Occupational medicine.

[50]  D. Vlahov,et al.  Hepatitis A among homosexual men and injection drug users: more evidence for vaccination. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[51]  J. Banatvala,et al.  HEPATITIS A : CHANGING PREVALENCE AND POSSIBLE VACCINES , 1991 .

[52]  N. Ciavarella,et al.  Long‐term immunogenicity and safety of an inactivated hepatitis A vaccine in haemophilic patients , 1996, Haemophilia : the official journal of the World Federation of Hemophilia.

[53]  M. Böttiger Long-term immunity following vaccination with killed poliovirus vaccine in Sweden, a country with no circulating poliovirus. , 1984, Reviews of infectious diseases.

[54]  P. Vandamme Hepatitis A: how to match prevention strategies to changing epidemiology , 2000 .

[55]  Hepatitis A vaccination programs in communities with high rates of hepatitis A. , 1997, MMWR. Morbidity and mortality weekly report.

[56]  L. Sagliocca,et al.  Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial , 1999, The Lancet.

[57]  Marjorie J. Miller Viral Taxonomy , 1993, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[58]  S. Kapoor,et al.  The changing epidemiological pattern of hepatitis A in an urban population of India: Emergence of a trend similar to the European countries , 2000, European Journal of Epidemiology.

[59]  P. van Damme,et al.  Cost‐effectiveness analysis of vaccination against hepatitis A in travellers , 1994, Journal of medical virology.

[60]  S. Millership,et al.  Antibody responses to Hepatitis A vaccine in healthy adults. , 2001, Communicable disease and public health.

[61]  H. Schätzl,et al.  Vaccination against hepatitis A: comparison of different short-term immunization schedules. , 1992, Vaccine.

[62]  H. Margolis,et al.  A multistate, foodborne outbreak of hepatitis A. National Hepatitis A Investigation Team. , 1999, The New England journal of medicine.

[63]  R. Dagan,et al.  Immunization against hepatitis A in the first year of life: priming despite the presence of maternal antibody. , 2000, The Pediatric infectious disease journal.

[64]  B. Genton,et al.  Inactivated hepatitis A vaccine booster given >/=24 months after the primary dose. , 2000, Vaccine.

[65]  S. Weber,et al.  Cost-Effectiveness of Hepatitis A Vaccination in Healthcare Workers , 1997, Infection Control & Hospital Epidemiology.

[66]  J. O'grady,et al.  Fulminant hepatitis in patients with chronic liver disease , 2000, Journal of viral hepatitis.

[67]  B. McMahon,et al.  A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine. , 1996, Archives of Pediatrics & Adolescent Medicine.

[68]  S. Lee Hepatitis A vaccination in patients with chronic liver disease in Taiwan , 2000, Journal of viral hepatitis.

[69]  M. Böttiger The elimination of polio in the Scandinavian countries. , 1993, Public health reviews.

[70]  R. Guan,et al.  Hepatitis A sero-epidemiology in Singapore: a changing pattern. , 1993, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[71]  F. Chang,et al.  Long-term follow-up of hepatitis A vaccination in children. , 1999, Vaccine.

[72]  B. Kaić,et al.  Hepatitis A control in a refugee camp by active immunization. , 2001, Vaccine.

[73]  Braddick Mr Travel-associated hepatitis A. , 1992 .

[74]  J. Hoofnagle,et al.  Viral hepatitis and liver disease , 1984 .

[75]  H. Glick,et al.  Economic evaluation of vaccination programmes: a consensus statement focusing on viral hepatitis. , 2002, PharmacoEconomics.

[76]  P Van Damme,et al.  Inactivated hepatitis A vaccine‐induced antibodies: Follow‐up and estimates of long‐term persistence , 2001, Journal of medical virology.

[77]  P. van Damme,et al.  The shift in prevalence of hepatitis A immunity in Flanders, Belgium. , 1998, Acta gastro-enterologica Belgica.

[78]  M. Buti,et al.  Hepatitis A and B in children and adolescents--what can we learn from Puglia (Italy) and Catalonia (Spain)? , 2000, Vaccine.

[79]  P. van Damme,et al.  The first combined vaccine against hepatitis A and B: an overview. , 1999, Vaccine.

[80]  M. Chang,et al.  Follow-up immunogenicity of an inactivated hepatitis A virus vaccine in healthy children: results after 5 years. , 1998, Vaccine.

[81]  F. Shaw,et al.  Use of hepatitis A vaccine in a community-wide outbreak of hepatitis A. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[82]  K. Herck,et al.  Long-term persistence of cellular immunity towards hepatitis A virus following hepatitis A virus vaccination , 2002 .

[83]  S. Iwarson,et al.  Excellent booster response 4 to 8 years after a single primary dose of an inactivated hepatitis A vaccine. , 2006, Journal of travel medicine.

[84]  P. van Damme,et al.  An economic evaluation of hepatitis A vaccination in Dutch military personnel. , 1998, Military medicine.

[85]  R Allard,et al.  Hepatitis A vaccination during an outbreak among gay men in Montréal, Canada, 1995–1997 , 2001, Journal of epidemiology and community health.

[86]  J. Parry,et al.  A collaborative case control study of sporadic hepatitis A in England. , 1995, Communicable disease report. CDR review.

[87]  M. Borg,et al.  Hospital laundry workers--an at-risk group for hepatitis A? , 1999, Occupational Medicine.

[88]  M. Piazza,et al.  Safety and immunogenicity of hepatitis A vaccine in infants: a candidate for inclusion in the childhood vaccination programme. , 1999, Vaccine.

[89]  J. Kruppenbacher,et al.  Does the concurrent administration of an inactivated hepatitis A vaccine influence the immune response to other travelers vaccines? , 2006, Journal of travel medicine.

[90]  P. Reinke,et al.  Immunogenicity and safety of hepatitis A vaccine in liver and renal transplant recipients. , 1999, The Journal of infectious diseases.

[91]  A. Tilzey,et al.  Hepatitis A vaccine responses in HIV-positive persons with haemophilia. , 1996, Vaccine.

[92]  G. Frösner,et al.  Placebo-controlled efficacy study of hepatitis A vaccine in Valdivia, Chile. , 1992, Vaccine.

[93]  A. Shattock,et al.  Cost-effective analysis of hepatitis a prevention in Ireland , 2000, American Journal of Gastroenterology.

[94]  M. Ferson,et al.  Notification of infectious diseases by general practitioners: a quantitative and qualitative study , 2000, The Medical journal of Australia.

[95]  J. Kazmierczak,et al.  Hepatitis A infections in Wisconsin: trends in incidence and factors affecting surveillance, 1986-1995. , 1998, Wisconsin Medical Journal.

[96]  M. Ferson,et al.  Changing epidemiology of hepatitis A in the 1990s in Sydney, Australia , 1998, Epidemiology and Infection.

[97]  S. Lemon,et al.  Public health control of hepatitis A: memorandum from a WHO meeting. , 1995, Bulletin of the World Health Organization.

[98]  F. André Randomized, cross-over, controlled comparison of two inactivated hepatitis A vaccines. , 2001, Vaccine.

[99]  B. Wiens,et al.  A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children. , 1992, The New England journal of medicine.

[100]  K. Reisinger,et al.  A prospective, randomized, comparative US trial of a combination hepatitis A and B vaccine (Twinrix) with corresponding monovalent vaccines (Havrix and Engerix-B) in adults. , 2001, Vaccine.

[101]  B. Feighner,et al.  Immunization of US soldiers with a two-dose primary series of inactivated hepatitis A vaccine: early immune response, persistence of antibody, and response to a third dose at 1 year. , 1995, The Journal of infectious diseases.

[102]  A. Safary,et al.  Interruption of an outbreak of hepatitis A in two villages by vaccination , 1994, Journal of Medical Virology.

[103]  S. Vento,et al.  Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C , 2000, Journal of viral hepatitis.

[104]  B. McMahon,et al.  Safety and immunogenicity of hepatitis A vaccine in patients with chronic liver disease , 1998, Hepatology.

[105]  B. Bell,et al.  Prevalence of antibody to hepatitis A virus in drinking water workers and wastewater workers in Texas from 1996 to 1997. , 2000, Journal of occupational and environmental medicine.

[106]  Tsang,et al.  Inactivated hepatitis A vaccine in Chinese patients with chronic hepatitis B infection , 1999, Alimentary pharmacology & therapeutics.

[107]  M. Jensenius,et al.  Prolonged nosocomial outbreak of hepatitis A arising from an alcoholic with pneumonia. , 1998, Scandinavian journal of infectious diseases.

[108]  S. Iwarson Are we giving too many doses of hepatitis A and B vaccines? , 2002, Vaccine.

[109]  A. Zanetti,et al.  Hepatitis A vaccination in chronic carriers of hepatitis B virus. , 1999, The Journal of pediatrics.

[110]  W. Wesołowski,et al.  Diabetes care management: a managed care approach. , 1998, WMJ : official publication of the State Medical Society of Wisconsin.

[111]  S. Millership,et al.  Control of a community hepatitis A outbreak using hepatitis A vaccine. , 1999, Communicable disease and public health.

[112]  H. Barros,et al.  A survey on hepatitis A in Portuguese children and adolescents , 1999, Journal of viral hepatitis.

[113]  P. Bonanni,et al.  Experience of hepatitis A vaccination during an outbreak in a nursery school of Tuscany, Italy , 1998, Epidemiology and Infection.

[114]  L. Theilmann,et al.  Hepatitis A vaccination: schedule for accelerated immunization. , 1992, Vaccine.

[115]  J. Stapleton,et al.  Hepatitis A virus-specific humoral and cellular immune responses following immunization with a formalin-inactivated hepatitis A vaccine. , 1999, Vaccine.

[116]  N. Bodsworth,et al.  The effect of immunization with inactivated hepatitis A vaccine on the clinical course of HIV‐1 infection: 1‐year follow‐up , 1997, AIDS.

[117]  A. Safary,et al.  Clinical assessment of the safety and efficacy of an inactivated hepatitis A vaccine: rationale and summary of findings. , 1992, Vaccine.

[118]  B. Bell,et al.  Sources of Infection Among Persons With Acute Hepatitis A and No Identified Risk Factors During a Sustained Community-Wide Outbreak , 2000, Pediatrics.

[119]  S. Hadler,et al.  A Community-wide epidemic of hepatitis A in Ohio. , 1986, American journal of epidemiology.

[120]  Ananya Das,et al.  An economic analysis of different strategies of immunization against hepatitis a virus in developed countries , 1999, Hepatology.

[121]  P. Matricardi,et al.  The changing epidemiology of hepatitis A in Italy. , 1993, The Italian journal of gastroenterology.

[122]  I. Bygbjerg,et al.  Hepatitis A vaccine. A new convenient single-dose schedule with booster when long-term immunization is warranted. , 1994, Vaccine.

[123]  A. Theamboonlers,et al.  The declining pattern of seroepidemiology of hepatitis A virus infection among adolescents in Bangkok, Thailand. , 1997, The Southeast Asian journal of tropical medicine and public health.