Decreased placental TLR3 is associated with hepatitis B virus vaccine responsiveness in infants born to HBsAg-positive mothers

Lina Wu; Gan Fu; Xiuyang Xu; Linzhu Yi; Tian Yao; Huili Wan; Junli Li; Bo Wang; Shuying Feng; Yongliang Feng; Hongxing Wang; Frank Tacke; Raymond Kwok; Keita Kai; Suping Wang

doi:10.21037/tp-23-266

Decreased placental TLR3 is associated with hepatitis B virus vaccine responsiveness in infants born to HBsAg-positive mothers

Transl Pediatr. 2023 Jun 30;12(6):1204-1212. doi: 10.21037/tp-23-266. Epub 2023 Jun 8.

Authors

Lina Wu^{1

2

3}, Gan Fu^{1

3}, Xiuyang Xu^{1

3}, Linzhu Yi^{1

3}, Tian Yao^{1

3}, Huili Wan², Junli Li², Bo Wang⁴, Shuying Feng⁴, Yongliang Feng^{1

3}, Hongxing Wang^{5

6}, Frank Tacke⁷, Raymond Kwok⁸, Keita Kai⁹, Suping Wang^{1

3}

Affiliations

¹ School of Public Health, Shanxi Medical University, Taiyuan, China.
² Department of Pathology, the First Hospital, Shanxi Medical University, Taiyuan, China.
³ Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, China.
⁴ Department of Obstetrics and Gynaecology, the Third People Hospital of Taiyuan City, Taiyuan, China.
⁵ Institute of Special Medical Sciences, School of Forensic Medicine, Shanxi Medical University, Taiyuan, China.
⁶ Division of Neuropsychiatry and Psychosomatics, Department of Neurology, Beijing Psychosomatic Disease Consultation Center, National Center for Neurological Disorders, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, China.
⁷ Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
⁸ Department of Medicine, Khoo Teck Puat Hospital, Singapore, Singapore.
⁹ Department of Pathology, Saga University Hospital, Saga, Japan.

Abstract

Background: Although hepatitis B vaccination has a significant impact on the reduction hepatitis B virus (HBV) infection, babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being poor responsive to the vaccine with unilluminated mechanism. Toll-like receptor 3 (TLR3) plays a vital role in placental immunity, which affects the immune response of these babies. This study investigated the role of placental TLR3 in the immune responses of babies born to HBsAg-positive mothers to the HBV vaccine.

Methods: One hundred pairs of HBsAg-positive mothers and their newborns were recruited. Maternal blood samples were collected before delivery, and placental tissues were collected after delivery. Newborns were administered standard passive and active immunoprophylaxis and followed up until the age of 1. Infant blood samples were collected at 1 year of age. Mothers and infants were tested for HBV serological markers and HBV DNA by electrochemiluminescence immunoassay and fluorescence quantitative polymerase chain reaction. respectively. Placental TLR3 was detected by immunohistochemistry and score in a semi-quantitative fashion, circulating cytokines in infants were detected by enzyme-linked immunosorbent assay. Infants with anti-HBs ≥100 and <100 mIU/mL were classified into the high-responsiveness group and the non- or hypo-responsiveness group.

Results: The TLR3 protein was expressed in all placentas. Compared with the high-responsiveness group, the expression of TLR3 in the non- or hypo-responsiveness group was significantly decreased (χ²=10.39, P=0.001). A non-conditional logistic regression model showed that the increased expression of placental TLR3 protein decreased the odds of HBV vaccine non- or hypo-responsiveness in the babies of HBsAg-positive mothers [OR =0.25 (95% CI: 0.11-0.58)], and this association remained significant after accounting for maternal factors, such as HBeAg and HBV DNA, as well as infant cytokines, including IL-6, IL-12, TNF-α, IFN-α, and IFN-γ [OR =0.15 (95% CI: 0.05-0.44)].

Conclusions: Decreased placental TLR3 expression is associated with impaired responsiveness to HBV vaccination in babies born to HBsAg-positive mothers.

Keywords: HBsAg-positive mother; Hepatitis B virus vaccine; non- or hypo-response; placenta; toll-like receptor 3 (TLR3).