https://orcid.org/0000-0001-8627-1263
Recently, a solicited letter requested further validation of our paper,Citation1 Seroconversion of hepatitis B surface antigen among successful immune response individuals in Southern China, published in Human Vaccines & Immunotherapeutics, July 2020. The authors stated that they were concerned about the high incidence (3.5%) of chronic hepatitis B virus (HBV) infection among those who had successfully received vaccinees over four years of data. Within the letter they listed four reasons to support their inquiry. This response letter offers our point-by-point responses sorted in the order as presented in the letter. Although we have responded to similar questions during the peer review process, we welcome the chance to answer them again. Thank you for the interest in our work.
First, the authors stated that the relatively high HBsAg prevalence (3.5%–5.3%) among those vaccinated in Long An County meant that a considerable proportion of participants had not received hepatitis B vaccination. In our study cohort, we collected demographic information from participants, including their name, parent name, gender, address, and birthday. In particular, vaccination date of each dose of hepatitis B (HB) vaccine was recorded for each individual in the cohort after the primary vaccination. Similar research efforts in Guangxi have followed this cohort to observe the long-term effectiveness of the HB vaccine for more than 30 years.Citation2–5 Therefore, based upon common record-keeping and rigorous clinical methods; we did not consider the possibility that the participants did not receive hepatitis B vaccination. Our study did focus on the timely vaccination of the first dose of HB vaccine within 24 hours, which may be the critical factor affecting the HBsAg prevalence in the vaccinated cohort. Unfortunately, this information was not available for analysis.
We addressed a similar question in the peer review process regarding the response of hepatitis B surface antibody (anti-HBs) after hepatitis B vaccination. Considering that the primary HB vaccination was delivered during 1987–1993 and the then-resources in Guangxi, Southern China, we could not guarantee the detection of the anti-HBs level for every participant. Alternatively, we provided the anti-HBs levels of the 143 participants in 2015 as the baseline data for our analyses.
Second, we agree that it was unusual that among the five individuals with HBsAg seroconversion, three had low HBsAg titles (1.3–2.8 IU/ml, Table 3 of the article). We considered that they might be in the early stage of the infection or the early convalescent stage of an acute infection. However, we could not address their infection stage because this study did not test for the IgM of hepatitis B core antibodies. We did consider the HBsAg seroconversion in the remaining two individuals even in the protection amounts of anti-HBs may be due to the mutation of HBV. However, we did not test the sequence of the HBV. We have acknowledged these issues, presented them as limitations in our paper, and regard these as the critical directions of future work.
Third, the authors wrote that the occurrence of HBsAg in individuals with positive anti-HBs was similar to that in those with negative anti-HBs (4.2% [2/48] vs 3.2% [3/95]), and it indicates that hepatitis B vaccination offered no long-term protection. Statistically, the authors raised a good point. However, further investigation of the existence of immune oppression and mutation of HBV is needed, and the investigation of the immune memory of T lymphocytes in both groups over time is essential.
Fourth, the authors stated that the prevalence of hepatitis B core antibody (anti-HBc) in 143 individuals in 2015 and 2019 was 23.1% and 7.7%, respectively (Table 2 of the article) and that this age-decline of anti-HBc prevalence is implausible. We have noticed this phenomenon and responded to a similar inquiry in the peer-review process. However, the decline of positive detection of anti-HBc did happen in this cohort. For example, the study results in 2015 indicated that the positive rate of anti-HBc dropped from 23.05% in participants born in 1988 to 14.88% in those born in 1992.Citation4 Another possible reason contributing to the decline from 2015 to 2019 in this study could have been the detection variability of test reagents from different test suppliers.
In summary, we thank the authors for their interest in our work. Researchers in Guangxi have more than 30-years’ experience in studying the effectiveness of the HBV vaccine in Long An, which is considered one of the earliest counties to deliver HB vaccine to newborns and infants on a county-territory scale in China. The study conducted among participants born in 1987–1993 in 2015 in Long An County indicated that the HBsAg positive rate was 3.5%;Citation5 meanwhile, another study performed among people born from 1987 to 1989 in Long An in 2016 indicated that the HBsAg prevalence was 4.9%.Citation6 Both the HBsAg positive rates were lower than the rate (5.3%) reported in our study.Citation7 The number of HBsAg positive rates in this cohort over-time indicated that breakthrough infections did occur. Furthermore, researchers in Italy have reported that children with a strong immune response to the HB vaccine have been infected by HBsAg-positive mothers or other HBsAg-positive household close contacts.Citation8,Citation9
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