Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders

• Published in: Vaccines (Basel) 2023-09, Vol.11 (9), p.1479
• Main Authors: Shiraishi, Kana, Yoshida, Osamu, Imai, Yusuke, Akbar, Sheikh Mohammad Fazle, Sanada, Takahiro, Kohara, Michinori, Miyazaki, Takashi, Kamishita, Taizou, Miyake, Teruki, Hirooka, Masashi, Tokumoto, Yoshio, Abe, Masanori, Rubido, Julio Cesar Aguilar, Nieto, Gerardo Guillen, Hiasa, Yoichi
• Format: Article
• Language: English
• Subjects: Adverse events; Antibodies; Antigens; carboxyl vinyl polymer; cellular immunity; Clinical trials; Core protein; Cytotoxicity; Dosage and administration; Enzymes; Genotype & phenotype; Health aspects; Hepatitis; Hepatitis B; Hepatitis B surface antigen; Hepatitis B vaccine; hepatitis B virus; Immunization; Immunoassay; Immunoglobulin A; Immunoglobulin G; Infections; infectious disease; Intranasal medication; Laboratories; Lymphocytes; Lymphocytes T; Methods; Neutralization; Neutralizing; Penicillin; Phosphatase; Polymers; Prevention; Vaccination; Vaccines; Vinyl polymers; Viruses; Viscosity
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines11091479

Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5–10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders.