Exploring the influence of maternally derived antibody against hepatitis B surface antigen on infants’ immune response to hepatitis B vaccine in mice

25 Background: Whether maternal anti-HBs acquired transplacentally plays a negative 26 role in newborn infants’ immune response to hepatitis B vaccine (HepB Vac), it remains 27 controversial and has not been paid enough attention. 28 Methods: 267 BALB/c mice were bred. All mice were divided into two groups according 29 to different doses of HepB Vac (2μg, 5μg) injected to mice. Each group was sub-divided 30 into three subgroups according to different doses of hepatitis B immunoglobulin (HBIG) 31 (50 IU, 25 IU, 0 IU) injected combined with the first dose of HepB Vac. Three doses of 32 HepB Vac were administrated at 0 week, 4week and 8 week respectively. Antibodies 33 against hepatitis B surface antigen (anti-HBs) were tested four weeks after the third 34 dose of HepB Vac. 35 Results: Among 267 mice, 40 were of low- and non-response to HepB Vac (anti-HBs ， 36 100 mIU/mL). Multivariate logistic regression analysis showed that rates of anti-HBs ， 37 100 mIU/mL were: 1.1%, 23.1% and 20.7% in groups of HBIG=0 IU(1), HBIG=25 IU(2) 38 and HBIG=50 IU(3) respectively, p = 0.002, and among subgroups, (1) vs (3), RR= 0.032, 39 95% CI [0.004, 0.255], p = 0.001, (2) vs (3), RR= 1.359, 95% CI [0.588, 3.144], p = 0.473; 40 4.5% and 25.6% in groups of HepB Vac 5μg and 2μg, RR=0.093, 95% CI [0.035, 0.250], 41 p <0.001; 6.1% and 23.7% in groups of intramuscular injection Conclusions: HBIG has a negative impact on both the rate of effective immune response and response level of anti-HBs, which preliminarily indicates maternal 47 anti-HBs inhibits infants’ immune response to HepB Vac.


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A new phenomenon has appeared that more and more child-bearing age women   standard feedstuff and drank purified water freely. The mice were exposed to a 12 hour 98 light -12 hour dark cycle at 22 ± 2 °C with relative humidity of 60% ± 5%. All mice

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Shandong Taibang Biological Products Co., LTD in China.

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ARCHITECT Anti-HBs Reagent Kit: produced by Abbott Ireland Diagnostics Division.

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Anti-HBs were performed by a chemiluminescence microparticle immunoassay 114 using ARCHITECT i 2000 full-automatic immune analysis system. The normal reference 115 value was set as 0-10 mIU/mL. One test was carried out for each sample.

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For the specimens of anti-HBs titer，1000 mIU/mL, they were diluted to 10 times, 20 117 times or 30 times, and so on, until anti-HBs levels fell below the upper limit of detection

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Grouping and Immunization Schedule

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Four weeks after the third dose of HepB Vac, blood was collected from the mice eye  172

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Among the 267 mice of 0-4-8 w schedule, the rate of low-and non-response to HepB

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Vac was significantly higher in the group with HBIG than group without HBIG; that was  Table 1.

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The effect of HBIG doses on anti-HBs levels was analyzed among the mice adopted 193 intramuscular injection in 0-4-8 w schedule. We just selected the mice in that group 194 because intramuscular injection is the route most commonly used in clinical settings.

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Among the three groups of different HBIG doses ， the mean anti-HBs titers decreased 196 gradually from HBIG 0 IU group to HBIG 50 IU group, and the differences were 197 statistically significant. That showed the same trend in both HepB Vac 2 μg group and

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HepB Vac 5 μ group. There was also significant difference in each pairwise comparison 10 199 except for the comparison between B and C (p，0.05). The above are shown in Table 2. factors related to high-response to HepB Vac among mice, as shown in Table 3.

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In recent years, some experts have already noticed that maternal antibodies

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The main results (Table 1,2) in this study were consistent with previous findings in

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In this study, we found that anti-HBs titer were at the level of 10 3 -10 6 255 log 10 mIU/mLwhen samples with anti-HBs ， 1000 mIU/mL were completed the dilution.

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Because long term persistence of anti-HBs protector titer have been related to higher

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Results in this study suggested that the lower dose of vaccine was the independent 262 risk factors resulted in low-and non-response of immunity (Table 1), and the higher 263 dose of vaccine was the independent factor that help to produce high immune response 264 ( the similar conclusion to the opinion got above.

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The correct vaccination route can achieves higher effect of immune response. By

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The limitation of the study is that the administration of HBIG is proposed to mimic with the antibody response of group of mother mice without HepB vaccination.

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Moreover, further studies are needed to optimize the conditions (i.e. HepB Vac dose,

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HBIG dose, injection schedule, and mice weight) that would help to refine the results.

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In conclusion, a dramatic reduction of HBV infection rate has reached because of