Insights into induction of the immune response by the hepatitis B vaccine

Abstract

After more than four decades of hepatitis B virus (HBV) vaccine implementation, its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved. Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth. All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications. However, there are still many drawbacks to overcome. The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization. Additionally, the current most widely used second-generation vaccines do not induce protective immunity in 5% to 10% of the population, particularly in people over 40-years-old, obese (body mass index > 25 kg/m²), heavy smokers, and patients undergoing dialysis or infection with human immunodeficiency virus. Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance, particularly in difficult settings. These advances re-launch the expectations of achieving the World Health Organization's objective of completing hepatitis control by 2030.

Keywords: Antibodies; Hepatitis B virus; Immune response; Neutralizing; Vaccine.

Figure 1

Recommended hepatitis B virus vaccination schemes. The hepatitis B immunization schedule is flexible, but minimal intervals and ages need to be observed. The recommended dose varies (5-40 μg of hepatitis B surface antigen protein/mL) depending on the individuals’ age and the vaccine brand. ^aMonovalent hepatitis B vaccine 0.5 mL must be used for the at birth immunization (HepB-BD). Immunocompromised adults or patients under dialysis require larger or additional doses of the hepatitis B vaccine; ^bCombined hepatitis B, diphtheria, tetanus, adsorbed acellular pertussis, inactivated poliovirus vaccine. This vaccine cannot be administered at birth, before 6 postnatal weeks, or at age ≥ 7 years; ^cHeplisav-B is a vaccine recently approved for adults; it has a novel adjuvant and its recommended schedule is two doses 1 mo apart. HepB3: Three doses of hepatitis B vaccine; HepB-BD: Monovalent single dose of the hepatitis B virus vaccine; HBIG: Hepatitis B Immunoglobulin.

Figure 2

Hepatitis B three doses of infant vaccine coverage and seroprevalence.Hepatitis B virus seroprevalence data is from Polaris Observatory Collaborators: Global Prevalence, Treatment, and Prevention of Hepatitis B Virus Infection in 2016: A Modelling Study. Lancet Gastroenterol Hepatol 2018; 3: 383–403. HBV: Hepatitis B virus.

Figure 3

Anti-hepatitis B surface antibodies titers by age. A: The anti-hepatitis B surface antibodies (anti-HBs) titer was determined in 765 blood donors. In 2000, vaccination against hepatitis B virus was included in the Argentine newborns’ National Vaccination Calendar. In 2003, the catch-up strategy for 11-year-old children was implemented. Therefore, individuals under 28-years-old are reached currently by the universal vaccine implementation. On average, protective levels of anti-HBs (> 10 mIU/mL) were detected in 75.2% of the population reached by universal vaccination (< 28-years-old) and in 32.2% of the not reached population (> 28-years-old); B: Anti-HBs kinetics. The anti-HBs titer was determined in 132 children born after 2000. In the first 2 years, the median anti-HBs titer fell from 196.2 mIU/mL to less than 10 mIU/mL (black line). Five years post-vaccination, about 20% of the population showed anti-HBs levels below 10 mIU/mL. aHBs: Anti-hepatitis B surface antibodies.