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Qu et al. Etiological prevention of liver cancer

prevalence and different maternal HBV status [79] . Results and accumulated evidence regarding the presence
from the investigations conducted in Taiwan [80,81] , in of immunologic memory by the booster test [79] , HBV
Thailand [82] , and in Qidong of China [83] indicated that a breakthrough infection still happened. For precise
notable proportion of fully vaccinated adolescents had prevention against chronic HBV infection, it is necessary
no or low immunological memories against HBsAg. All to understand the human immune responses to HBV
enrolled populations in these studies received infantile vaccine in different individuals with distinct HBV
HBV vaccination and lived in high HBV endemic areas. exposure status in the prenatal period. Recently, it has
Because the duration and uniformity of this immunologic been demonstrated that the immunological response
memory after primary vaccination at infancy is uncertain, pattern to microbes/microbial products in the HBV-
these studies would suggest a necessary consideration exposed neonates was very different from the healthy
of 1 or 2 booster doses. However, other studies ones. Prenatal exposure to HBV induced complex
conducted in Italy [78] , that enrolled participants who changes in the newborn’s immune system [89] . Follow-up
were all born to HBsAg-negative mothers, and in Hong studies worldwide have demonstrated that children were
Kong [84] , that enrolled children who received primary well protected after HBV vaccination. More evidence is
HBV vaccination at ages 3 months to 11 years, found needed regarding the adolescent booster effect against
significant anamnestic response among the vaccinated HBV infection based on different maternal HBsAg-
populations. Based on the percentage of the anamnestic carrying status.
responders, these investigators suggested that the
primary vaccination confers lifelong protection against HBsAg has been detected in amniotic fluid, cord
HBV infection and no booster is needed [78,79 ,84,85] . blood, breast milk, vaginal fluids, and infant gastric
content [64,90] . According to the immune selection theory,
HBV breakthrough infection in young adults may occur T cells that recognize the epitopes in HBsAg with high-
if the immunologic memory to HBsAg is absent upon affinity receptors (TCR) might be deleted during immune
sexual, or horizontal exposure including household HBV system development [91] . Basic immunology studies
exposure [86] . The setting of booster tests conducted in have revealed that the differentiation and proliferation of
different studies was different. It is still questionable specific antibody producing B cells was regulated by a
whether all the adolescents uniformly remain protected distinct T cell subset, the follicular helper T cells (Tfh) [92] .
against HBV infection when they were engaged in more Although the murine immune system is different from that
social activities. The duration and immunologic memory of humans, we can understand the potential implication
status after primary vaccination might be different when from the murine immune responses to model antigen.
they were born to mothers with different maternal status Experimental data by using the I-Ek-restricted helper T
and the ages of vaccination received. In the last decade, cell response of B10.BR mice to pigeon cytochrome c, the
reports of HBV infection among the vaccinated young tractable protein vaccination model for studying different
adults have been documented [87,88] . A study conducted
in Qidong of China, that enrolled a total of 2,919 young TCR affinities, demonstrated that significantly more T
adults aged 19-21 years who received plasma-derived cells with high affinity TCR developed into “resident”
neonatal HBV vaccination found a total of 124 (4.2%, Tfh cells in vivo than the T cells with low affinity TCR,
124/2,289) participants were HBsAg negative, but and the low affinity clonotypes of T cells failed to form
double positive for anti-HBs and anti-HBc [HBsAg(-) & memory [93,94] . The experimental data revealed that Tfh
anti-HBs(+) & anti-HBc(+)]. None of them were positive function was regulated by the strength of T cell antigen
for HBeAg or for anti-HBe or for anti-HCV. Notably, receptor binding, i.e. TCR affinity. Therefore, the function
7/124 (5.65%) individuals with seromarkers of HBsAg(-) of Tfh and the B cell memory after primary vaccination
& anti-HBs(+) & anti-HBc(+) had serum ALT ≥ 40 U/mL [87] . in the individuals born to healthy mothers should not
Serum levels of HBV DNA were quantified among the be the same as those born to HBsAg-positive mothers
124 individuals, and 14/124 (11.3%) of them had > and those born to HBeAg- & HBsAg-positive mothers.
10,000 copies/mL, 37/124 (29.8%) of them had 500- Currently, no data is documented about the difference.
10,000 copies/mL, and 73/124 (58.9%) were below the
detection limitation. The longitudinal follow-up studies Sexual contact is an important pathway for HBV
found that some of the vaccinated children became transmission in low HBV endemic areas [86] . Universal
infected with HBV in adulthood when they lost anti-HBs neonatal HBV vaccination significantly reduces the
at childhood [83,87] . HBsAg seroprevalence, and horizontal exposure will
be the major route of HBV infection. Because of the
Adolescent booster to children born to controversial conclusion regarding immune protection
HBsAg-positive mothers decreased the risk of the uninfected children/adolescents who had serum
of HBV infection anti-HBs < 10 mIU/mL, it is still uncertain whether all
Although investigators worldwide have determined the children who were protected by primary vaccination

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