World’s first malaria vaccine to be rolled out in pilot-projects in Africa (17 November 2016)

The World Health Organization (WHO) has secured funding for the pilot-deployment of the malaria vaccine RTS, S in 3 to 5 settings in sub-Saharan Africa.

This follows a commitment of US$ 15 million for the malaria vaccine pilots, assuring full funding for the first phase of the programme. Earlier this year, Gavi, the Vaccine Alliance and UNITAID announced commitments of up to US$ 27.5 million and US$ 9.6 million, respectively, for the first 4 years of the vaccine programme.

RTS, S acts against P. falciparum, the most deadly malaria parasite globally, and the most prevalent in Africa. It was developed through a partnership between GlaxoSmithKline and the PATH Malaria Vaccine Initiative (MVI), with support from the Bill & Melinda Gates Foundation and from a network of African research centers.

The pilot programme will evaluate

  • the feasibility of delivering the required 4 doses of RTS,S;
  • the impact of RTS,S on lives saved; and
  • the safety of the vaccine in the context of routine use.

It will also assess the extent to which the vaccine’s protective effect demonstrated in children aged 5–17 months old in the Phase 3 trial can be replicated in real-life settings.

RTS,S is the first malaria vaccine to successfully complete pivotal Phase 3 testing. The Phase 3 trial enrolled more than 15,000 infants and young children in 7 countries in sub-Saharan Africa. Countries that participated in the Phase 3 clinical trials will be prioritized for inclusion in the WHO pilot programme.

The RTS,S vaccine is proposed as a tool to complement the existing package of WHO-recommended malaria preventive, diagnostic and treatment measures and will be used in combination with the current interventions. Other tools include:

  • long-lasting insecticidal bed-nets,
  • spraying inside walls of dwellings with insecticides,
  • preventive treatment for infants and during pregnancy,
  • prompt diagnostic testing, and
  • treatment of confirmed cases with effective anti-malarial medicines.

As RTS,S is only partially effective, it will be essential that any vaccinated patients with a fever be tested for malaria, and that all those with a confirmed malaria diagnosis are treated with high quality, effective anti-malarial medicines.

The Vaccine

Name: RTS,S/AS01 (RTS,S)

Type:  Pre-erythrocytic stage hybrid recombinant protein vaccine, based on the RTS,S recombinant antigen

Description: It comprises the hybrid polypeptide RTS in which regions of the P. falciparum circumsporozoite protein known to induce humoral (R region) and cellular immune (T region) responses are covalently bound to the hepatitis B surface antigen (S).

This recombinant fusion protein (RTS) is expressed in Saccharomyces cerevisiae together with free hepatitis B surface antigen (S), to form RTS,S virus-like particles.

The formulation comprises 25µg of RTS,S with the AS01E adjuvant system. This novel adjuvant system contains the immunomodulatory molecules 3-O-desacyl-f4-monophosphoryl lipid A (MPL) and a saponin derived from the bark of the Quillaja saponaria tree (QS21) together with liposomes.

The RTS,S antigen is formulated, lyophilized and reconstituted with the liquid AS01 adjuvant system prior to administration.

The pharmaceutical form corresponds therefore to a powder (RTS,S) and a suspension (AS01) for reconstitution for injection.

Composition:

  • RTS,S antigen,
  • excipients: sucrose, polysorbate 80, disodium phosphate dihydrate, and sodium dihydrogen phosphate dehydrate.

The suspension includes, in addition to the MPL and QS-21 immuno-enhancer components, additional excipients:

  • dioleoyl phosphatidylcholine (DOPC),
  • cholesterol,
  • sodium chloride,
  • disodium phosphate.

Presentation: 2-dose glass vial of RTS,S powder to be reconstituted with a 2-dose glass vial of AS01 adjuvant system suspension.

Reconstitution and Dose: After reconstitution the total volume is 1mL, of which 0,5 mL represents 1 vaccine dose to be administered intramuscularly.

No preservative is included in either RTS,S formulation or AS01E adjuvant system. The vials should therefore be discarded at the end of the vaccination session, or within 6 hours after opening, whichever comes first.

Administration: 0.5mL of reconstituted vaccine administered by intramuscular injection in deltoid

Storage: 2–8 °C

Schedule: 4 dose schedule recommended between 5-17 months

Vaccine efficacy (4 dose schedule):

  • clinical malaria: 39%
  • severe malaria: 31.5%

Duration of protection: robust protection for 6 months, then wanes

Precautions and side effects:

  • The vaccine is not effective against vivax malaria
  • Excess cases of meningitis and cerebral malaria noted among vaccinees, but causal relationship not yet established
  • Risk of febrile seizures during the first 7 days after vaccination
  • Not recommended for children younger than 5 months based on Phase 3 trial data- low vaccine efficacy

Useful Links:

Link to the WHO news release:

http://www.who.int/mediacentre/news/releases/2016/funding-malaria-vaccine/en/

Link to the WHO position paper on the RTS,S vaccine:

http://www.who.int/wer/2016/wer9104.pdf?ua=1

 

Link to WHO question and answer page on the RTS,S vaccine:

http://www.who.int/immunization/research/development/malaria_vaccine_qa/en/

Link to the manufacturer’s fact sheet on the RTS, S vaccine:

http://www.malariavaccine.org/sites/www.malariavaccine.org/files/content/page/files/RTSS%20vaccine%20candidate%20Factsheet_FINAL.pdf

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