Immune response to the hepatitis B antigen in the RTS,S/AS01 malaria vaccine, and co-administration with pneumococcal conjugate and rotavirus vaccines in African children: A randomized controlled trial

Abstract

The RTS,S/AS01 malaria vaccine (Mosquirix) reduces the incidence of Plasmodium falciparum malaria and is intended for routine administration to infants in Sub-Saharan Africa. We evaluated the immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix) and human rotavirus vaccine (HRV; Rotarix) when co-administered with RTS,S/AS01 (www.clinicaltrials.gov NCT01345240) in African infants. 705 healthy infants aged 8–12 weeks were randomized to receive three doses of either RTS,S/AS01 or licensed hepatitis B (HBV; Engerix B) vaccine (control) co-administered with diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type-b-conjugate vaccine (DTaP/Hib) and trivalent oral poliovirus vaccine at 8–12-16 weeks of age, because DTaP/Hib was not indicated before 8 weeks of age. The vaccination schedule can still be considered broadly applicable because it was within the age range recommended for EPI vaccination. PHiD-CV or HRV were either administered together with the study vaccines, or after a 2-week interval. Booster doses of PHiD-CV and DTaP/Hib were administered at age 18 months.Non-inferiority of anti-HBV surface antigen antibody seroprotection rates following co-administration with RTS,S/AS01 was demonstrated compared to the control group (primary objective). Pre-specified non-inferiority criteria were reached for PHiD-CV (for 9/10 vaccine serotypes), HRV, and aP antigens co-administered with RTS,S/AS01 as compared to HBV co-administration (secondary objectives). RTS,S/AS01 induced a response to circumsporozoite protein in all groups. Pain and low grade fever were reported more frequently in the PHiD-CV group co-administered with RTS,S/AS01 than PHiD-CV co-administered with HBV. No serious adverse events were considered to be vaccine-related. RTS,S/AS01 co-administered with pediatric vaccines had an acceptable safety profile. Immune responses to RTS,S/AS01 and to co-administered PHiD-CV, pertussis antigens and HRV were satisfactory.

A Universal Plug-and-Display Vaccine Carrier Based on HBsAg VLP to Maximize Effective Antibody Response

“…Another advantage of using HBsAg as vaccine carrier is the potential value of antibodies against such a carrier: once proven that they do not impact the antigen-specific response, these antibodies could be beneficial against HBV infection. For example, the RTS,S/AS01 vaccine induces in human HBsAg-specific antibody response non-inferior to EngerixB R vaccination (39); however, RTS,S has only 20% of HBsAg genetically fused to the CSP-based antigen, leaving the VLP well-exposed to the immune system. Differently, a new vaccine candidate R21, composed solely by HBsAg genetically fused to a C-terminal portion of CSP, does not induce anti-HBsAg antibodies in mice; this is related to inaccessibility of the HBsAg, masked by the antigen (40).…”

Multi-functional antibodies are induced by the RTS,S malaria vaccine and associated with protection in a phase I/IIa trial

“…Greater efficacy might be achieved by modification of RTS,S or developing new vaccines [10]. Considering RTS,S has been subject to extensive clinical testing and can be safely co-administered with other vaccines as part of standard childhood immunisation programs [3,[11][12][13][14], working towards improving RTS,S is an attractive option.…”

Long-term immunogenicity and immune memory response to the hepatitis B antigen in the RTS,S/AS01E malaria vaccine in African children: a randomized trial

“…6 In 2016, the World Health Organization (WHO) recommended pilot implementation of the vaccine in children as of 5 months of age in 3 to 5 moderate-to-high malaria transmission settings in Sub-Saharan Africa. 7 Primary study results, published in Valéa et al 8 support the indication of the RTS,S/AS01 E vaccine for immunization of infants against hepatitis B in settings where prevention of P. falciparum malaria is also being sought. These results demonstrated that RTS,S/AS01 E was non-inferior to a licensed HepB vaccine in terms of anti-HBs seroprotection rates at one month post-primary vaccination.…”

“…Details about the coadministered vaccines can be found in the Table 1. Data for participants receiving the different RTS,S/AS01 E (RTS,S groups) or HepB (control groups) primary vaccination regimens (both co-administered in various combinations with different study vaccines), 8 were pooled in RTS,S groups and Table 1. Demographic characteristics per primary vaccination with RTS,S/AS01 E or HepB and co-administered vaccines (ATP cohort for immunogenicity -FU2).…”

“…RTS,S/AS01 E when co-administered with PHiD-CV, HRV and other vaccines included in the EPI had an acceptable safety profile during the 26 month follow-up period. 8 As part of the long-term follow-up of this phase III study, we assessed long-term antibody persistence and safety of the RTS,S/AS01 E vaccine (up to 48 months post-primary vaccination series), the presence of anti-HBs immune memory and the anti-HBs immune response to HepB booster vaccination given 4 years after primary vaccination.…”