Hepatitis B specific T cell immunity induced by primary vaccination persists independently of the protective serum antibody level

Abstract

In 2005, in accordance with recommendations made by the European Medicines Agency, the Italian Drug Agency ordered withdrawal of the hexavalent Hexavac(®) vaccine (Sanofi Pasteur MSD) from the market. Concerns had been raised about the low immunogenicity of the hepatitis B virus component of the vaccine, assessed by measurement of serum antibody levels, and its potential consequences on long-term protection against hepatitis B infection. We evaluated memory T cell response to establish whether there are differences in the protective mechanisms among children who had received either Hexavac(®) or Infanrix-hexa(®) (GlaxoSmithKline) as their primary vaccination. Immunological memory was determined by measuring the ability of T cells to proliferate and secrete IFNγ by ELISA and intracellular cytokines (IFNγ and IL-2) when cultured with hepatitis B surface antigen (HBsAg). The different memory subsets of T cells were also measured. The results indicate that, although they generate different serum antibody levels, both vaccines are efficient in generating T recall responses in vitro five years after the primary vaccination. The less immunogenic Hexavac(®) vaccine induces a strong T antigen response, as indicated by increased blast proliferation and the enhanced presence of memory subsets after HBsAg recall stimulation. These findings suggest that cellular immune response should be considered alongside serological markers as a surrogate of protection.

Short- and Long-Term Effects of a Challenge Dose of Hepatitis B Vaccine in Individuals With and Without Residual Anti-HBs

“…5 Recent data suggest the presence of cellular immunity in vaccinated individuals without residual antiHBs. 6,7 Although the role of cellular immunity is not well understood, epidemiological data show that individuals not infected at the time of vaccination almost never develop acute clinical or chronic hepatitis B. 5,8 In conclusion, our results and those from Spradling et al suggest that there is no need for boosters in vaccinated individuals with residual anti-HB antibodies.…”

Comparing Humoral and Cellular Immune Response Against HBV Vaccine in Kidney Transplant Patients

“…Further epidemiological data support the notion that HBV-specific memory T cells might compensate for a lack of humoral protection (15).…”

Hepatitis B Virus Vaccine–Induced Cell-Mediated Immunity Correlates with Humoral Immune Response following Primary Vaccination during Infancy

“…Other studies reported a lack of T cell proliferative responses to HBsAg among nonresponders to HBV vaccine booster dose (19)(20)(21). Although one study reported that infant nonresponders to primary vaccination secreted less IFN-g than responders (22), the correlation between anti-HBs levels and IFN-g production remained inconclusive, as this finding was confirmed in some (23) but refuted in other studies (14,24,25). In one study in infants, nonresponders to primary vaccination against HBV secreted less IL-10 than responders (22).Similar results have been observed in adult populations (23,26,27).…”