The role of new hepatitis B vaccines in South Africa


  • G U van Zyl Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa
  • T Maponga Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa
  • H Rabie Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Tygerberg Children’s Hospital, Cape Town, South Africa
  • J Taljaard Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Tygerberg Academic Hospital, Cape Town, South Africa



Hepatitis B virus, Vaccines, South Africa, Immunogenicity, HIV, Diabetes Mellitus


Vaccination is key to eliminating hepatitis B virus infection in South Africa (SA). Despite introducing immunisation in 1995, as part of the expanded programme of immunisation (EPI), hepatitis B virus infection remains endemic, and EPI vaccine coverage is incomplete. In addition to infants, non-immune adults at risk of infection through their occupation or with behavioural risk factors should receive vaccination. SA has many individuals with diabetes mellitus (a prevalence of almost 13%), obesity, HIV (8.45 million) or older age (5 million >60 years old), associated with a poorer vaccine response. Recently two new hepatitis B vaccines have been licensed: HEPLISAV-B includes an adjuvant that improves immunogenicity and has shown improved vaccine response in individuals with HIV, old age or diabetes mellitus. PreHevbrio, which includes three hepatitis B surface protein domains, instead of one, may also be more immunogenic, although clinical study data are still limited. These two novel vaccines have not yet been investigated in children and licensed in SA. Should HEPLISAV-B become available in SA, it may be particularly valuable to target high-risk groups in the country, such as people living with HIV, who show a poor response to the currently licensed vaccine.


South African National Government. People of South Africa. Pretoria: SA government: 2023. https:// (accessed 1 November 2023).

Joint United Nations Programme on HIV/AIDS. Fact sheet. Latest global and regional statistics on the status of the AIDS epidemic. Geneva: UNAIDS, 2022. documents/2022/UNAIDS_FactSheet (accessed 18 November 2022).

Maepa MB, Ely A, Kramvis A, et al. Hepatitis B virus research in South Africa. Viruses 2022;14(9):1939.

AnderssonMI,MapongaTG,IjazS,etal.TheepidemiologyofhepatitisBvirusinfectioninHIV-infected and HIV-uninfected pregnant women in the Western Cape, South Africa. Vaccine 2013;31(47):5579- 5584.

Thumbiran NV, Moodley D, Parboosing R, Moodley P. Hepatitis B and HIV co-infection in pregnant women: Indication for routine antenatal hepatitis B virus screening in a high HIV prevalence setting. S Afr Med J 2014;104(4):307-309.

Blumberg BS. Australia antigen and the biology of hepatitis B. Science 1977;197(4298):17-25. https://

Blumberg BS. Hepatitis B virus, the vaccine, and the control of primary cancer of the liver. Proceedings of the National Academy of Sciences 1997;94(14):7121-7125.

Scolnick EM, McLean AA, West DJ, McAleer WJ, Miller WJ, Buynak EB. Clinical evaluation in healthy

adults of a hepatitis B vaccine made by recombinant DNA. JAMA 1984;251(21):2812-2815.

Burnett RJ, Kramvis A, Dochez C, Meheus A. An update after 16 years of hepatitis B vaccination in

South Africa. Vaccine 2012;30:C45-C51.

Joseph Davey D, Hsiao N-Y, Wendy Spearman C, et al. Low prevalence of hepatitis B virus infection in HIV-uninfected pregnant women in Cape Town, South Africa: Implications for oral pre-exposure

prophylaxis roll out. BMC Infect Dis 2022;22(1):a719.

Mbenenge N, Subramoney K, Gascua Adu-Gyamfi C, Treurnicht FK. Hepatitis B virus immunity gap: A six-year laboratory data review of hepatitis B serological profiles in Gauteng Province, South Africa. Adv Virol 2023;2023:6374874.

Prabdial-Sing N, Makhathini L, Smit SB, et al. Hepatitis B sero-prevalence in children under 15 years of age in South Africa using residual samples from community-based febrile rash surveillance. PLoS ONE 2019;14(5):e0217415.

Vermeulen M, Swanevelder R, Van Zyl G, Lelie N, Murphy EL. An assessment of hepatitis B virus prevalence in South African young blood donors born after the implementation of the infant hepatitis B virus immunisation program: Implications for transfusion safety. Transfusion 2021;61(9):2688-2700.

Lacombe K, Gozlan J, Boelle P-Y, et al. Long-term hepatitis B virus dynamics in HIV-hepatitis B virus- co-infected patients treated with tenofovir disoproxil fumarate. AIDS 2005;19(9):907-915. https://doi. org/10.1097/01.aids.0000171404.07995.5c

Hamers RL, Zaaijer HL, Wallis CL, et al. HIV–HBV coinfection in Southern Africa and the effect of lamivudine- versus tenofovir-containing cART on HBV Outcomes. J Acquired Immune Defic Syndr 2013;64(2):174-182.

Funk AL, Lu Y, Yoshida K, et al. Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: A systematic review and meta-analysis. Lancet Infect Dis 2021;21(1):70-84.

Buti M, Manzano ML, Morillas RM, et al. Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies: The Preblin study. PLoS ONE 2017;12(9):e0184550.

Mizushima D, Takano M, Aoki T, et al. Effect of tenofovir-based HIV pre-exposure prophylaxis against HBV infection in men who have sex with men. Hepatology 2023;77(6):2084-2092. https://doi. org/10.1097/HEP.0000000000000384

Samsunder N, Ngcapu S, Lewis L, et al. Seroprevalence of hepatitis B virus: Findings from a population- based household survey in KwaZulu-Natal, South Africa. Int J Infect Dis 2019;85:150-157. https://doi. org/10.1016/j.ijid.2019.06.005

Andersson MI, Rajbhandari R, Kew MC, et al. Mother-to-child transmission of hepatitis B virus in sub-Saharan Africa: Time to act. Lancet Glob Health 2015;3(7):e358-e359. S2214-109X(15)00056-X

Amponsah-Dacosta E, Lebelo RL, Rakgole JN, Burnett RJ, Selabe SG, Mphahlele MJ. Evidence for a change in the epidemiology of hepatitis B virus infection after nearly two decades of universal hepatitis B vaccination in South Africa. J Med Virol 2014;86(6):918-924.

Tsebe KV, Burnett RJ, Hlungwani NP, Sibara MM, Venter PA, Mphahlele MJ. The first five years of universal hepatitis B vaccination in South Africa: Evidence for elimination of HBsAg carriage in under 5-year-olds. Vaccine 2001;19(28):3919-3926.

Breakwell L, Tevi-Benissan C, Childs L, Mihigo R, Tohme R. The status of hepatitis B control in the African region. Pan Afr Med J 2017;27(Suppl 3):S17. 24. Mdlalose N, Parboosing R, Moodley P. The prevalence of hepatitis B virus infection in HIV-positive and HIV-negative infants: KwaZulu-Natal, South Africa. Afr J Lab Med 2016;5(1):283-287. https://doi.


South African National Department of Health. National Guidelines for the Management of Viral Hepatitis. Pretoria: NDoH, 2019.

Razwiedani LL, Mogale NM, Mawela MPB. Hepatitis B vaccination coverage amongst healthcare workers in a tertiary academic hospital in Gauteng province, South Africa. South Afr J Infect Dis 37(1):a393.

World Health Organization. Hepatitis B vaccines: WHO position paper – recommendations. Vaccine 2010;28(3):589-590.

Solomon-Rakiep T, Olivier J, Amponsah-Dacosta E. Weak adoption and performance of hepatitis B birth-dose vaccination programs in Africa: Time to consider systems complexity? A scoping review. Trop Med Infect Dis 2023;8(10):474.

Spearman CW, Afihene M, Ally R, et al. Hepatitis B in sub-Saharan Africa: Strategies to achieve the 2030 elimination targets. Lancet Gastroenterol Hepatol 2017;2(12):900-909. S2468-1253(17)30295-9

Whittle H, Jaffar S, Wansbrough M, et al. Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. BMJ 2002;325(7364):569-573. bmj.325.7364.569

Mendy M, Peterson I, Hossin S, et al. Observational study of vaccine efficacy 24 years after the start of hepatitis B vaccination in two Gambian villages: No need for a booster dose. PLoS ONE 2013;8(3):e58029.

Siriaksorn S, Puthanakit T, Sirisanthana T, Sirisanthana V. Prevalence of protective antibody against hepatitis B virus in HIV-infected children with immune recovery after highly active antiretroviral therapy. Vaccine 2006;24(16):3095-3099.

Catherine F-X, Piroth L. Hepatitis B virus vaccination in HIV-infected people: A review. Hum Vaccin Immunother 2017;13(6):1304-1313.

Bodsworth NJ, Cooper DA, Donovan B. The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B virus carrier state. J Infect Dis 1991;163(5):1138-1140.

Yang S, Tian G, Cui Y, et al. Factors influencing immunologic response to hepatitis B vaccine in adults. Sci Rep 2016;6(1):27251.

Tian Y, Hua W, Wu Y, et al. Immune response to hepatitis B virus vaccine among people living with HIV: A meta-analysis. Front Immunol 2021;12:745541.

Champion CR. Heplisav-B: A hepatitis B vaccine with a novel adjuvant. Ann Pharmacother


Grundlingh N, Zewotir TT, Roberts DJ, Manda S. Assessment of prevalence and risk factors of diabetes

and pre-diabetes in South Africa. J Health Popul Nutr 2022;41(1):7-19.


Statistics South Africa. SA’s elderly population increasing steadily. Pretoria: Stats SA, 2023. https:// (accessed 1 November 2023).


through early booster response in college students. Hepatology 2010;51(5):1547-1554. https://doi.


Yanny B, Konyn P, Najarian LM, Mitry A, Saab S. Management approaches to hepatitis B virus vaccination nonresponse. Gastroenterol Hepatol 2019;15(2):93-99.

Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014;103(2):137-149.

Awad AM, Ntoso A, Connaire JJ, et al. An open-label, single-arm study evaluating the immunogenicity and safety of the hepatitis B vaccine HepB-CpG (HEPLISAV-B) in adults receiving hemodialysis. Vaccine 2021;39(25):3346-3352.

US Food and Drug Adminsitration. HEPLISAV-B. FDA, 2023. biologics/vaccines/heplisav-b (accessed 1 November 2023).

European Medicines Agency. Heplisav B. EMA, 2020. human/EPAR/heplisav-b (accessed 1 November 2023).

Jackson S, Lentino J, Kopp J, et al. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine 2018;36(5):668-674.

Marks KM, Kang M, Umbleja T, et al. Immunogenicity and safety of hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HEPLISAV-B) in HBV vaccine-naive people with HIV. Clin Infect Dis 2023:ciad201.

Khaimova R, Fischetti B, Cope R, Berkowitz L, Bakshi A. Serological response with Heplisav-B in prior hepatitis B vaccine non-responders living with HIV. Vaccine 2021;39(44):6529-6534. https://doi. org/10.1016/j.vaccine.2021.09.050

Talbird SE, Anderson SA, Nossov M, Beattie N, Rak AT, Diaz-Mitoma F. Cost-effectiveness of a 3-antigen versus single-antigen vaccine for the prevention of hepatitis B in adults in the United States. Vaccine 2023;41(23):3506-3517.

European Medicines Agency. PreHevbri. EMA, 2022. human/EPAR/prehevbri (accessed 1 November 2023).

Vesikari T, Finn A, van Damme P, et al. Immunogenicity and safety of a 3-antigen hepatitis B vaccine vs a single-antigen hepatitis B vaccine: A phase 3 randomized clinical trial. JAMA Netw Open 2021;4(10):e2128652.

Raven SFH, Hoebe CJPA, Vossen ACTM, et al. Serological response to three alternative series of hepatitis B revaccination (Fendrix, Twinrix, and HBVaxPro-40) in healthy non-responders: A multicentre, open-label, randomised, controlled, superiority trial. Lancet Infect Dis 2020;20(1):92-101.






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van Zyl GU, Maponga T, Rabie H, Taljaard J. The role of new hepatitis B vaccines in South Africa. S Afr Med J [Internet]. 2024 Feb. 13 [cited 2024 Jul. 14];114(2):e1473. Available from:

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