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

Hum Vaccin Immunother. 2018 Jun 3;14(6):1489-1500. doi: 10.1080/21645515.2018.1442996. Epub 2018 Apr 13.

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.

Keywords: RTS,S; co-administration; hepatitis B; immunogenicity; malaria; plasmodium falciparum; pneumococcal conjugate vaccine; vaccine.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa South of the Sahara
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Female
  • Fever / epidemiology
  • Humans
  • Immunization Schedule*
  • Immunogenicity, Vaccine*
  • Incidence
  • Infant
  • Malaria Vaccines / administration & dosage*
  • Malaria Vaccines / adverse effects
  • Malaria Vaccines / immunology
  • Male
  • Pain / epidemiology
  • Pneumococcal Vaccines / administration & dosage*
  • Pneumococcal Vaccines / adverse effects
  • Pneumococcal Vaccines / immunology
  • Rotavirus Vaccines / administration & dosage*
  • Rotavirus Vaccines / adverse effects
  • Rotavirus Vaccines / immunology
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology
  • Vaccines, Synthetic / administration & dosage*
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology

Substances

  • Malaria Vaccines
  • PHiD-CV vaccine
  • Pneumococcal Vaccines
  • RIX4414 vaccine
  • RTS,S-AS01 vaccine
  • Rotavirus Vaccines
  • Vaccines, Attenuated
  • Vaccines, Synthetic

Associated data

  • ClinicalTrials.gov/NCT01345240

Grant support

The study was sponsored by GlaxoSmithKline Biologicals SA (GSK). GSK was involved in all stages of the study conduct and analysis and GSK funded the study and all costs associated with the development and the publishing of the present manuscript. All authors had full access to the data and the corresponding author was responsible for submission of the publication.