Long-term immunogenicity and immune memory response to the hepatitis B antigen in the RTS,S/AS01_E malaria vaccine in African children: a randomized trial

Abstract

RTS,S/AS01 E malaria vaccine contains the hepatitis B virus surface antigen and may thus serve as a potential hepatitis B vaccine. To evaluate the impact of RTS,S/AS01 E when implemented in the Expanded Program of Immunization, infants 8-12 weeks old were randomized to receive either RTS,S/AS01 E or a licensed hepatitis B control vaccine (HepB), both co-administered with various combinations of the following childhood vaccines: diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b, trivalent oral poliovirus, pneumococcal non-typeable Haemophilus influenzae protein D conjugate and human rotavirus vaccine. Long-term persistence of antibodies against the circumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) were assessed, together with the immune memory response to the HB antigen following a booster dose of HepB vaccine. Subgroups receiving RTS,S or the HepB control vaccine were pooled into RTS,S groups and HepB groups, respectively. One month post-HepB booster vaccination, 100% of participants in the RTS,S groups and 98.3% in the control groups had anti-HBs antibody concentrations ≥10 mIU/mL with the geometric mean concentrations (GMCs) at 46634.7 mIU/mL (95% CI: 40561.3; 53617.6) and 9258.2 mIU/mL (95% CI: 6925.3; 12377.0), respectively. Forty-eight months post-primary vaccination anti-CS antibody GMCs ranged from 2.3 EU/mL to 2.7 EU/mL in the RTS,S groups compared to 1.1 EU/mL in the control groups. Hepatitis B priming with the RTS,S/AS01 E vaccine was effective and resulted in a memory response to HBsAg as shown by the robust booster response following an additional dose of HepB vaccine. RTS,S/AS01E when co-administered with PHiD-CV, HRV and other childhood vaccines, had an acceptable safety profile. ARTICLE HISTORY

Antibody responses to the RTS,S/AS01E vaccine and Plasmodium falciparum antigens after a booster dose within the phase 3 trial in Mozambique

“…Although the booster dose did increase IgG, IgG1, IgG3 and IgG4 antibodies, the increments were lower than those of anti-CSP antibodies, and were similar to the response induced by primary vaccination in the Manhiça site 7 . Interestingly, the results of a trial that analyzed the response to a hepatitis B vaccine booster after RTS,S primary vaccination showed an increased response in HBsAg IgG concentrations compared to primary vaccination 24 . The responses to HBsAg may be an indication of the quality of the immune response or the immune status of the child and the capacity to respond to vaccination and it requires further investigation.…”

Antibody avidity, persistence, and response to antigen recall: comparison of vaccine adjuvants

“…Finally, these effects can be antigen-dependent and at least partially specific to HBsAg. Indeed, specific antibody responses to RTS,S/AS01 E vaccine (circumsporozoite [CS] malaria antigen on an HBsAg carrier) were significantly less durable for CS than for HBsAg 48 , despite the induction of CS-specific memory B cells and T-helper cells 49 , 50 . We conclude that from a quantitative perspective, the benefit of using a specific adjuvant or AS lies in maximizing the peak response, to prolong the duration of protection when immunity wanes over time (Fig.…”

Pre-Erythrocytic Vaccines against Malaria

“…The humoral and cellular immune responses generated by the RTS, S/AS01 vaccine were shown to offer immunity to mosquito bite challenge infections in human trials [ 22 , 23 ]. The RTS, S/AS01 vaccination also generated protective immune responses against Hepatitis B, in addition to against malaria [ 24 ].…”