Hepatitis A Vaccines – Impact of Universal Childhood Vaccination Programmes
Table 2: Properties of Commonly Available Combination Hepatitis A Virus Vaccines Vaccine
Manufacturer TWINRIX™ AMBIRIX™ Vaccine HAV Antigen Dose
Combination (Manufacturer’s Guidelines) Paediatric Adult
GlaxoSmithKline Biologicals HAV + HBV 360 EI.U† Rixensart, Belgium
GlaxoSmithKline Biologicals HAV + HBV 720 EI.U Rixensart, Belgium
VIATIM™/ VIVAXIM™
HEPATYRIX™ GlaxoSmithKline Biologicals HAV + typhoid NA Rixensart, Belgium Sanofi Pasteur
HAV + typhoid NA Marcy l’Etoile, France
*For full immunisation against HAV, a booster dose omonovalentvaccine should be given 6–12 months after vaccination. †Enzyme-linked immunosorbent assay (ELISA) units.
HAV = hepatitis C virus; HBV = hepatitis B virus; NA = not applicable; U = units.
individuals all HAV vaccines are highly immunogenic, but considerably less so (10- to 100-fold) than HAV infection.8
Although both the proportion of seropositive people and levels of antibodies decline somewhat prior to the second ‘booster’ dose (see Figure 2), completion of the two-dose schedule confers up to 100% seropositivity8,27,28 extremely rare.29
Protective efficacy is almost universal.30,31 Conventionally, a
Between two and four weeks after the first ‘priming’ dose of a conventional two-dose vaccination schedule, 90–100% of vaccinated people become seropositive for anti-HAV antibodies (see Figure 2).8,27,28
and non-responding individuals are The
absolute lower limit of anti-HAV antibodies required to convey seroprotectivity is currently unknown due to the limitations of the available anti-HAV detection immunoassays.8
serum concentration of ≥10mIU/ml, depending on immunoassay, is used to signify seroprotection but individuals may be protected even in the absence of detectable antibodies.6
vaccines does not appear to affect immunogenicity.32,33
Interchangeability between There is some
evidence that even substantial delays between doses do not prevent full immunisation (see Table 3),34–37
and that immunity can be
induced, at least in the short term, following only a single dose of vaccine.38,39
Such flexibility in the vaccination schedule could prove extremely beneficial but the two-dose schedule remains the standard and is probably crucial for the induction of long-term protection. Long-term persistence of anti-HAV antibodies ≥15 years after the standard immunisation schedule has been demonstrated (Van Herck and Van Damme, personal communication),40–43
and
mathematical models predict protective antibody levels persisting for ≥25 years in 95% of the vaccinees.44–47
In addition to antibody
persistence, hepatitis A vaccination also induces immune memory that could outlast antibody production and confer lifelong immunity.9 HAV vaccines have an excellent safety profile, with mild local injection-site reactions the most frequently reported side effect, and no serious adverse side effects have been definitively ascribed to HAV vaccination.8
Hepatitis A Immunisation Strategies Immunisation strategies vary considerably and are dependent on continued seroprevalence studies, surveillance of changes in epidemiology, the availability of resources and cost–benefit analyses. Strategies broadly fall into three areas: pre-exposure prophylaxis through the vaccination of individuals in high-risk groups, post-exposure control of sporadic outbreaks or individual exposure and universal childhood immunisation.
EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW 102
Figure 2: Seroconversion Rates and Anti-hepatitis A Virus Antibody Levels Following Vaccination in Immunocompetent Individuals
104 100 75 103 50 25 101
01020 Weeks post primary vaccination
30 40 50 0 60
Seroconversion rates and anti-hepatitis A virus (HAV) immunoglobulin G (IgG) antibody geometric mean concentration in immunocompetent individuals following conventional two-dose vaccination at 0 and 26 weeks with HAVRIXTM. Adapted with permission from Schmidtke et al., 2005.28
Immunisation of Individuals in High-risk Groups Traditionally, immunisation policies have targeted populations thought to be at high-risk of infection, including travellers, men who have sex with men, those with chronic liver disease or blood clotting disorders, injecting drug users and some occupational groups.48
Prior to the
vaccination era, military personnel, especially those from non-endemic areas of HAV, were seen as a high-risk group due to overcrowding and the unsanitary conditions typical of military life, and were therefore an obvious group for pre-exposure prophylactic vaccination.49–53
720 EI.U NA Volume (ml)
Paediatric Adult 0.5
1.0 1.0 1440 EI.U NA 160 U NA NA 1.0 1.0
Number of Schedule Doses
(Months) 3 2 1 1 0, 1, 6 0, 6–12 0* 0*
However, it
is now apparent that the susceptibility of the military is most likely due to their services in areas of high endemicity.10
Furthermore, although
some groups are recognised as being at elevated risk of infection, in up to 50% of cases no risk factors for infection can be determined.4,54
As a
result, targeting high-risk populations is unlikely to lead to a sustained reduction in disease incidence or widespread public immunity.
Post-exposure Control of Community-wide Outbreaks Vaccination as a control measure during sporadic and prolonged community-wide outbreaks can be extremely successful. The effectiveness of HAV vaccines as post-exposure prophylactics was demonstrated soon after their initial development. An outbreak in two villages in Slovakia had an apparent incidence of >2,000
79
Seroconversion (%)
Anti-HAV IgG (GMC) mIU/MI-1
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