Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP.

Abstract

BACKGROUND:

The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector.

METHOD:

Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara-vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls.

RESULTS:

No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected.

CONCLUSIONS:

The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types.

CLINICAL TRIALS REGISTRATION:

NCT01883609.

• Authors: Tommy Rampling, Katie J Ewer, Georgina Bowyer, Carly M Bliss, Nick J Edwards, Danny Wright, Ruth O Payne, Navin Venkatraman, Eoghan de Barra, Claudia M Snudden, Ian D Poulton, Hans de Graaf, Priya Sukhtankar, Rachel Roberts, Karen Ivinson, Rich Weltzin, Bebi-Yassin Rajkumar, Ulrike Wille-Reece, Cynthia K Lee, Christian F Ockenhouse, Robert E Sinden, Stephen Gerry, Alison M Lawrie, Johan Vekemans, Danielle Morelle, Marc Lievens, Ripley W Ballou, Graham S Cooke, Saul N Faust, Sarah Gilbert, Adrian V S Hill
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 214 Issue 5 Pg. 772-81 (Sep 01 2016) ISSN: 1537-6613 [Electronic] United States
• PMID: 27307573 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Chemical References

• Drug Carriers
• Malaria Vaccines
• Protozoan Proteins
• RTS,S-AS01B vaccine
• Vaccines, Combined
• Vaccines, Synthetic
• thrombospondin-related adhesive protein, protozoan

Topics

• Adenoviridae (genetics)
• Adolescent
• Adult
• Animals
• Drug Carriers
• Drug-Related Side Effects and Adverse Reactions (epidemiology, pathology)
• Female
• Healthy Volunteers
• Humans
• Immunization Schedule
• Malaria Vaccines (administration & dosage, adverse effects, immunology)
• Malaria, Falciparum (prevention & control)
• Male
• Middle Aged
• Protozoan Proteins (administration & dosage, immunology)
• Treatment Outcome
• Vaccines, Combined (administration & dosage, adverse effects, immunology)
• Vaccines, Synthetic (administration & dosage, immunology)
• Vaccinia virus (genetics)
• Young Adult