Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines

Abstract

BackgroundMalaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination.DiscussionThe Malaria Vaccine Technology Roadmap’s goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%’. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine.ConclusionsSelecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine.

Research priorities for the development and implementation of serological tools for malaria surveillance

“…The RTS,S vaccine is the most advanced malaria vaccine, now in phase three clinical trials, and is based on P. falciparum CSP [38,39]; if the vaccine was to be licensed, CSP would not be an ideal candidate for sero-surveillance tests.…”

Preclinical Studies on a New Vaccine Formulation of BK-SE36, a Malaria Vaccine Candidate

“…This pre-erythrocytic vaccine (based on the circumsporozoite protein and hepatitis B surface antigen fusion protein) induces approximately 30-50% reduction in the risk of clinical malaria. Thus, a vaccine with higher levels of protection is still sought 6) . A blood-stage vaccine, either alone or as a component of a multi-stage vaccine, is needed to protect against clinical disease or epidemic malaria.…”

Use of Immunodampening To Overcome Diversity in the Malarial Vaccine Candidate Apical Membrane Antigen 1

“…There are currently no licensed vaccines for malaria; however, the development of clinical immunity in naturally exposed individuals suggests that a vaccine that reduces the morbidity and mortality associated with malaria is likely to be achievable (1). RTS,S/ASO1, a vaccine targeting the preerythrocytic stages of P. falciparum, is showing partial efficacy in a large multicenter phase III trial in Africa (2), but ultimately, an improved vaccine with higher efficacy and longer duration of protection will be required (3). This may be achieved through new vaccine approaches or by incorporating one or more asexual blood-stage antigens into a vaccine containing RTS,S.…”