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GMZ2 –Malaria vaccines

Source: TropIKA

Title of the session: GMZ2 –Malaria vaccines

Date: 03 November 2009

Agenda item: Symposium 14

Session theme: Malaria Vaccines

Meeting room: Shimba

Chair(s): James Oloo/AMANET; Brenda Okech/ GMZ2 Consortium

Presenters:

1. Micheal Thiesen/Statens Serum Institute, Copenhagen, Denmark
2. Mordmuller Benjamin
3. Saadou Issifou/Albert Sweitzer Hospital, Gabon
4. Saadou Issifou/ Albert Sweitzer Hospital, Gabon
5. Sanie Sesay for Kalifa Bojang/MRC Gambia
6. Ramadhani Noor/AMANET

TropIKA rapporteur: Onikepe Folarin

Major topics:

• The rational selection of the two subcomponents, GLURP and MSP3, in the GMZ2 candidate vaccine
• Results- Phase Ia clinical trial in German adults
• Results- Phase Ia clinical trial in Garbonese adults
• Results- Phase Ib dose finding pediatric trial in Gabonese children
• Results- Baseline studies in preparation for the proposed phase IIb multicenter efficacy clinical trial
• Clinical development strategy and the planned multicenter phase IIb efficacy clinical trial

Keywords: Vaccine, GLURP, MSP3, clinical trial, Phase I, Phase IIb,

Scope: The scope of presentations is about the hybrid GMZ2 vaccine and the outcome of the phase Ia and Ib clinical trials.

REPORT ON ORIGINAL SESSION

Overview

The session started with a brief overview of the GMZ2 consortium which is an integrated project for fostering research capacity strengthening, networking and project management and clinical trials of candidate vaccine GMZ2. The consortium consists of seven partners in Denmark, Germany, The Gambia, Gabon, Uganda, Burkina Faso and Tanzania.

In the study on the rationale for combining GLURP and MSP3 to form a hybrid vaccine known as GMZ2, an approach based on study of natural immunity was employed. The aim of the study was to develop a recombinant subunit vaccine against the blood stage of the parasite that will reduce or prevent the clinical manifestations by disrupting parasite development process or mimic the natural immunity. GLURP and MSP3 were selected based on human immune response to P. falciparum. The clinical trial of the individual vaccine candidates in Dodowa, Ghana showed high levels of IgG1 and/or IgG3 to GLURP and MSP3 and was associated with protection against clinical disease in children. GLURP and MSP3 were also considered because of its easy reproducibility, immunogenicity, ability of the specific IgG to inhibit parasite growth, strong ADCI effect and relative amino acid sequence conservation. In the clinical trial on the effectiveness of the hybrid GMZ2 vaccine candidate compared with GLURP and MSP3 alone, the IFA and antibody titer level were observed to be significantly higher in early days than the individual vaccine candidates.

Qualities of a good vaccine, basically the safety and efficacy, were observed in the outcome of the phase Ia GMZ2 vaccine clinical trials carried out in malaria naïve adults in Germany and phase Ib trials in adults and children aged 1-5years in Lambarene, Gabon. The vaccine was given in 3 different doses monthly for one year. End points such as humoral response efficacy, local and systemic reactions and serious adverse events (SAE) were determined. The studies showed that the hybrid vaccine was well tolerated with all local and systemic reactions disappearing after 3 days

CONTEXT AND ISSUE

Key facts and figures

The rationale for the various studies carried out in these presentations was to develop a safe and effective vaccine that will not be rendered ineffective by the parasite ability to change its cloth after its exposure.

Initiatives on the ground; experience/s derived

• Cross immunoelectrophoresis of soluble antigens was used to identify major antigens including GLURP and MSP3

• ELISA analysis was used to measure the antibody titer levels in the determination of the immunogenicity of the vaccine

• A randomized open-labeled dose escalating phase Ia clinical trial and randomized controlled double blind phase Ia and Ib clinical trials were employed in the malaria naïve adults and malaria endemic adults and children study respectively.

Lessons learned

Hybrid vaccine candidates such as GMZ2 will be a more effective and long lasting vaccine than individual candidates.

Issues raised, obstacles, difficulties

The need to search for other vaccine candidates, development of more hybrid vaccine was raised. Other issues raised were the need to learn from other vaccines successfully produced such as hepatitis B vaccine as it might give background knowledge to malaria vaccine.

Obstacles and difficulties experienced in the clinical trials were compliance by the volunteers the various level of reactions as they call for extra attention and care on the volunteers.

Future plans

The future plan is to move on to the phase IIb clinical trials in children. Efforts are on-going by the consortium to begin the trial by the end of the first quarter 2010. Part of the presentations in the session included preparations by 4 sites in Gambia, Uganda, Burkina Faso and Gabon. A total of 2240 children are anticipated for this trial based on epidemiology, transmission and base line survey.

FINDINGS AND CONCLUSIONS

From formal presentations

Hybrid vaccine will be the best vaccine that will be effective, safe and long lasting

Public health Implications

If an effective and safe vaccine is developed then malaria burden particularly in children will be reduced significantly and that will have effect on the MDG 6

Knowledge gap created

• The need to search for more vaccine candidates and production of more hybrid vaccine for clinical trials.

• The best route of administration of GMZ2 needs to be evaluated

From open discussions/debates

• The need for more funding in order to search for more vaccine candidates

• There is a call for researchers to decide on what question to be answered either to create vaccine to protect against infectivity or development of the disease

• What were the outcomes of previous vaccine candidates and what lessons were learnt from them.

Main points of agreement

The urgent need for a malaria vaccine in order to meet the MDGs 3, 4, 5 and most especially 6to find more vaccine candidates.

Recommendations

• Best method of temperature determination as fever is one of the symptoms of malaria

• Best route of administration of GMZ2 vaccine

Personal observations from rapporteur

The outcome of the phase II clinical trials of GMZ2 vaccines needs to be followed up

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