Hepatitis A vaccine explained

Hepatitis A vaccine is a vaccine that prevents hepatitis A.^{[1] [2]} It is effective in around 95% of cases and lasts for at least twenty years and possibly a person's entire life.^[3] If given, two doses are recommended beginning after the age of one.^[1] It is given by injection into a muscle.^[1] The first hepatitis A vaccine was approved in Europe in 1991, and the United States in 1995.^[4] It is on the World Health Organization's List of Essential Medicines.^{[5] [6]}

The World Health Organization (WHO) recommends universal vaccination in areas where the disease is moderately common.^[1] Where the disease is very common, widespread vaccination is not recommended as all people typically develop immunity through infection during childhood.^[1] The US Centers for Disease Control and Prevention (CDC) recommends vaccinating:^[7]

• All children aged 12–23 months
• Unvaccinated children and adolescents aged 2–18 years
• International travelers
• Men who have sex with men
• People who use injection or non-injection drugs
• People who have occupational risk for infection
• People who anticipate close contact with an international adoptee
• People experiencing homelessness
• People with HIV
• People with chronic liver disease
• Any person wishing to obtain immunity

In addition, a person who has not previously received hepatitis A vaccine and who has direct contact with someone with hepatitis A should get hepatitis A vaccine within two weeks after exposure.^[8]

Severe side effects are very rare. Pain at the site of injection occurs in about 15% of children and half of adults. Most hepatitis A vaccines contain inactivated virus while a few contain weakened virus. The ones with weakened virus are not recommended during pregnancy or in those with poor immune function. A few formulations combine hepatitis A with either hepatitis B or typhoid vaccine.

Soreness or redness where the shot is given, fever, headache, tiredness, or loss of appetite can happen after hepatitis A vaccine. As with any medicine, there is a very remote chance of a vaccine causing a severe allergic reaction, other serious injury, or death.^[8]

Medical uses

Within the US, the vaccine "Vaqta" developed by Maurice Hilleman and his team at Merck & Co. was licensed in 1995.^{[9] [10] [11]} The vaccine was phased in, around 1996, for children living in high-risk areas. In 1999, its usage was spread to areas with elevating levels of infection. In the US, the vaccine is strongly recommended for all children 12 to 23 months of age in an attempt to eradicate the virus nationwide. Although the original Food and Drug Administration (FDA) license for Havrix by GlaxoSmithKline is dated in 1995,^[12] it had been approved in Europe in 1991.^[13]

The US Centers for Disease Control and Prevention (CDC), recommends vaccination of all children over one year of age, people whose sexual activity puts them at risk, people with chronic liver disease, people who are being treated with clotting factor concentrates, people working in close proximity to the virus, and people who are living in communities where an outbreak is present.^[14] Hepatitis A is the most common vaccine-preventable virus acquired during travel,^[15] so people traveling to places where the virus is common like the Indian subcontinent, Africa, Central America, South America, Asia, and Eastern Europe should be vaccinated.^[16]

The vaccine is given in the muscle of the upper arm, in two doses for the best protection. The initial dose of the vaccine should be followed up by a booster six to twelve months later. Protection against hepatitis A begins approximately two to four weeks after the initial vaccination. Protection lasts at least 15 years and is estimated to last at least 25 years if the booster is administered.^[17]

A Cochrane review found that both types of vaccines offer significant protection, for at least two years using the inactivated vaccine and at least five years with the attenuated vaccine. The review concluded that the inactivated vaccine is safe, but required more high quality evidence to assess the safety of the attenuated vaccine.^[18]

Commercial vaccines

Several commercial hepatitis A vaccines are available. The definition of (U)nits varies among manufacturers depending on how hepatitis A antigen is measured in their products.

• Avaxim: made by Sanofi Pasteur. Inactivated hepatitis A virus produced in MRC-5 cells. Each dose contains 160U of antigen adsorbed on aluminium hydroxide (0.3 mg Al).^[19]
• Epaxal: made by Crucell. Also sold under the brand names HAVpur and VIROHEP-A. This vaccine consists of virosomes, artificial particles composed of synthetic lipids and influenza proteins in addition to the hepatitis A antigen. It does not contain aluminium.^[20]
• Havrix: made by GlaxoSmithKline. Inactivated hepatitis A virus produced in MRC-5 cells. Each adult dose contains 1440 ELISA units of viral antigen adsorbed on aluminium hydroxide (0.5 mg Al). The pediatric (child) doses contain half the amount of viral antigen and aluminium.^[21]
• Healive: made by Sinovac. Inactivated hepatitis A virus cultured in human diploid cell, followed by harvest, purification, inactivation, and aluminium adsorption. Each adult dose contains 500U of viral antigen. The pediatric dose contains 250U of viral antigen.
• Vaqta: made by Merck. Inactivated hepatitis A virus produced in MRC-5 cells. An adult dose contains 50U of antigen adsorbed onto 0.45 mg of aluminium (as aluminium hydroxyphosphate sulfate); a child dose contains half the amounts of antigen and aluminium.^[22]
• Biovac-A: made by Pukang, sold under the brand name Biovac-A in India and under the brand names Mevac-A in Guatemala, Philippines, Bangladesh, Nepal, Uzbekistan and Chile etc. It is a freeze-dried live attenuated hepatitis A vaccine. Hepatitis A virus H2 strain is produced in human diploid cells. A pack of 0.5ml vial of Biovac-A and 0.5ml ampoule of SWFI (sterile water for injection), contains not be less than 6.5 Lg CCID50. Only a single dose is needed. It is recommended by the WHO. Long term persistence research data predicated that sero-conversion remained and antibody titre was not less than 128IU/ml, 15 years after vaccination.

Combination vaccines

• Hepatitis A and B vaccine is a vaccine against hepatitis A and hepatitis B.^[23]
• Hepatitis A and typhoid vaccine is a vaccine against hepatitis A and typhoid.^{[24] [25] [26] [27]}

Further reading

• Book: Immunisation against infectious disease . Chapter 17: Hepatitis A . https://www.gov.uk/government/publications/hepatitis-a-the-green-book-chapter-17 . Public Health England . Ramsay M . 2013 .
• Book: U.S. Centers for Disease Control and Prevention (CDC) . Epidemiology and Prevention of Vaccine-Preventable Diseases . Hall E, Wodi AP, Hamborsky J, Morelli V, Schillie S . 14th . Washington D.C. . 2021 . Chapter 9: Hepatitis A . https://www.cdc.gov/vaccines/pubs/pinkbook/hepa.html .

Notes and References

1. ((World Health Organization)) . WHO position paper on hepatitis A vaccines – June 2012 . Weekly Epidemiological Record . 2012 . 87 . 28/29 . 261–76 . 22905367 . 10665/241938 . free . World Health Organization .
2. ((World Health Organization)) . WHO position paper on hepatitis A vaccines – October 2022 . Weekly Epidemiological Record . 2022 . 97 . 40 . 493–512 . 10665/363397 . free . World Health Organization .
3. Web site: Hepatitis a Q&As for Health Professionals | CDC. 19 January 2022.
4. Book: Patravale V, Dandekar P, Jain R . Nanoparticulate drug delivery perspectives on the transition from laboratory to market. 2012. Woodhead Pub.. 9781908818195. 1. publ.. Oxford. 212.
5. Book: World Health Organization model list of essential medicines: 21st list 2019. ((World Health Organization)). World Health Organization. 2019. Geneva. 10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. World Health Organization. free.
6. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 22nd list (2021) . 2021 . 10665/345533 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2021.02 . free .
7. Nelson NP, Weng MK, Hofmeister MG, Moore KL, Doshani M, Kamili S, Koneru A, Haber P, Hagan L, Romero JR, Schillie S, Harris AM . [<!-- Official URL --> https://www.cdc.gov/mmwr/volumes/69/rr/pdfs/rr6905a1-H.pdf Prevention of Hepatitis A Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2020 ]. MMWR. Recommendations and Reports . 69 . 5 . 1–38 . July 2020 . 32614811 . 8631741 . 10.15585/mmwr.rr6905a1 .
8. Web site: Hepatitis A Vaccine Information Statement . Centers for Disease Control and Prevention (CDC) . October 2021 . 13 July 2022.
9. Web site: Hepatitis A: Vaccine Licensed History of Vaccines. 6 February 2021. historyofvaccines.org. en.
10. Tulchinsky TH . 2018. Maurice Hilleman: Creator of Vaccines That Changed the World. Case Studies in Public Health. 443–470. 10.1016/B978-0-12-804571-8.00003-2. 7150172. 9780128045718.
11. Web site: Materials Documenting the Contribution of Dr. Maurice Hilleman to the Millennium Time Capsule Ceremony. 14 February 2021. National Museum of American History. en.
12. Web site: Hepatitis A Vaccine Information . Vaccine Information . ImmunizationInfo . 19 June 2008 . dead . https://web.archive.org/web/20070630091756/http://www.immunizationinfo.org/vaccineInfo/vaccine_detail.cfv?id=3 . 30 June 2007.
13. Web site: Hepatitis A Vaccine - an overview ScienceDirect Topics. 14 February 2021. sciencedirect.com.
14. Web site: Hepatitis A Vaccine: What you need to know . Vaccine Information Statement . Centers for Disease Control and Prevention (CDC) . 21 March 2006 . 12 March 2007 . live . https://web.archive.org/web/20071120133442/http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-hep-a.pdf . 20 November 2007.
15. Web site: Hepatitis, Viral, Type A . Travelers' Health: Yellow Book (CDC) . 12 March 2007 . dead . https://web.archive.org/web/20070328034621/http://www2.ncid.cdc.gov/travel/yb/utils/ybGet.asp?section=dis&obj=hav.htm . 28 March 2007.
16. Web site: Hepatitis A: Introduction . NHS Direct . 10 October 2006 . 12 March 2007 . https://web.archive.org/web/20070310143748/http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=667 . 10 March 2007 . dead.
17. Ott JJ, Irving G, Wiersma ST . Long-term protective effects of hepatitis A vaccines. A systematic review . Vaccine . 31 . 1 . 3–11 . December 2012 . 22609026 . 10.1016/j.vaccine.2012.04.104. free .
18. Irving GJ, Holden J, Yang R, Pope D . Hepatitis A immunisation in persons not previously exposed to hepatitis A . Cochrane Database Syst Rev . 7 . 7. CD009051 . 2012 . 22786522 . 10.1002/14651858.CD009051.pub2. 6823267 .
19. http://www.medicines.org.uk/emc/medicine/17385/PIL/AVAXIM/ Patient Information Leaflet
20. http://www.crucell.com/Products-Epaxal Epaxal
21. https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM224555.pdf Full Prescribing Information
22. Web site: VAQTA (Hepatitis A Vaccine, Inactivated). U.S. Food and Drug Administration (FDA). 7 February 2014. 11. live. https://web.archive.org/web/20150221023153/https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM110049.pdf. 21 February 2015.
23. Web site: Twinrix . U.S. Food and Drug Administration (FDA) . 3 October 2019 . 18 October 2020.
24. Web site: Australian Product Information – Vivaxim (Salmonella typhi Vi polysaccharide and hepatitis A virus antigen) Vaccine . 18 October 2020 .
25. Web site: Vivaxim Salmonella typhi vaccine; Hepatitis A vaccine . 6 March 2020 . 18 October 2020 .
26. Web site: Vivaxim 1mL injection syringe composite pack . Therapeutic Goods Administration (TGA) . 18 October 2020 . 19 October 2020 . https://web.archive.org/web/20201019104651/http://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=82745 . dead .
27. Web site: Summary for ARTG Entry: 82745 Vivaxim 1mL injection syringe composite pack . Therapeutic Goods Administration (TGA) . 18 October 2020 .