Malaria represents one of the world community’s most pressing public health problems. Every year, malaria kills hundreds of thousands of people from worlds poorest of countries, especially in the African region. However, Asia, Latin America, and to a lesser extent the Middle East and parts of Europe are also affected. According to WHO factsheet, in 2016, 212 million new cases were registered to result in 0.43 million deaths across the globe hitting hardest in the African region bearing 90 % of the total malaria burden.
The disease parasite spread by mosquito bite is a leading cause of death and illness among young children. Particularly vulnerable to disease are unborn children through infected pregnant women, which result in anaemia, low birth weight, premature birth and infant deaths. Children who survive this fiery disease do not escape unharmed; episodes of fever and anaemia often affects their physical and mental development. Even adults are not spared by this menacing disease, and debilitating fever can often remove them from the workplace or offices for days or even weeks at a time.
Early diagnosis and treatment of malaria reduce deaths and transmissions. The best available treatment for malaria is chemotherapy and work on a vaccine against malaria is ongoing, but in the meantime, the only preventive measure is to avoid the mosquito using mosquito nets and insecticide sprays. The malaria parasite is complex and has evolved over several centuries to survive every human effort to kill it. A frightening example of parasite adaption is its increased tolerance to drugs-which is swiftly emasculating chemotherapy in malaria-affected regions. Therefore, we need many tools to defeat this disease, tools that save lives today and those with the potential to save lives in the future.
Why a vaccine?
Vaccines prepare the immune system to respond to a pathogen that may be encountered at a later time. Suppression of malaria, rather than a cure remains a realistic regime for now but a vaccine would be an essential and a better tool for stopping the disease because:
- The current fight against the disease is being conducted on multiple fronts, including the distribution of bed-nets, indoor spraying, and the development of new medicines and insecticides. A vaccine would help close the gap left by these interventions.
- Malaria parasite and mosquitos routinely develop resistance to drugs, therefore, relying on chemotherapy for a lifetime is not an ideal solution.
- Vaccines have offered a cost-effective and potent means of preventing disease and death.
- People get weary of taking medication.
- Even a modestly efficacious malaria vaccine could protect hundreds of thousands of people from the disease each year.
Therapeutic Malaria vaccine
Malaria vaccine development is nearly six decades old and started in the 1960s from immunization studies of mice with inactivated parasite forms and currently, more than 10 vaccines candidates are in early stages of a clinical trial. Owing to its complexity, the malaria parasite is not an easy foe to eradicate or develop a vaccine against and therefore, has triggered multiple diverse strategies to control the disease. Most researchers believe that an effective vaccine strategy may require simultaneous or sequential use of several different approaches and a few promising strategies are described below.
Whole parasite vaccines
Many infectious diseases, such as smallpox and rubella, have been successfully controlled using live, attenuated virus vaccines. In malaria, the idea is to disable a living parasite using radiations or genetic mutations, while preserving its ability to challenge the immune system. These disabled parasites when delivered into the human body via mosquito bite, provided high levels (~ 90%) of protection, generating hope and excitement for a vaccine. However, this favourable outcome is marred by the requirement of 1000 mosquito bites to generate a high level of efficacy, which is impractical for public health use. Also, in the case of genetically disabled parasites lack irradiation raises concerns over safety.
Hybrid type vaccine
RTS, S vaccine is a hybrid malaria vaccine is currently the most advanced vaccine produced by Glaxo-SmithKline (GSK), is commercially known as ‘Mosquirix’. The vaccine was genetically engineered, which is the fusion of parasite protein (RT) and a viral protein (S) produced in yeast (S). This vaccine is promising and has demonstrated a 50% efficacy in children between the ages of 5 and 17 months and only a 30% efficacy in infants aged 6 to 12 weeks. In July 2015, European malaria vaccine agency approved the RTS, S vaccine as the first licensed malaria vaccine for children living in malaria risk areas in sub-Saharan Africa. However, some very recent developments suggest that RTS, S vaccine may need further modifications to increase its potency in inducing immunity against malaria sustained over a longer duration.
In this approach DNA encoding parasite protein is applied topically in a water-based solution. In 2014, Invio Pharmaceuticals introduced a DNA vaccine whose results are could give RTS a run for its money. Results show that the DNA vaccine, which encodes multiple parasite antigens (proteins) induces a better quality immune response and durable protection in non-human models than any of the previous vaccine in a trial. The promise of laboratory results has now spurred phase II clinical trials for this DNA vaccine.
Is there a malaria vaccine on the horizon?
The short answer, according to experts, is “we are closer to finding one”, however, the truth is that there is no approved, full-proof malaria vaccine available. It appears that the search for a malaria vaccine has entered a dynamic new phase. There is a strong possibility of a malaria vaccine and it is likely that a variety of different types of malaria vaccines shall be licensed in the coming years. In addition, new efforts are being accelerated to create further types of a malaria vaccine. An example is a transmission-blocking vaccine useful for reducing transmission further in low transmission areas for malaria eradication. Not only are researchers devising ever more novel methods of combating malaria, but roadmaps and business models are also being constantly developed to address the problem of inadequate funding and resources. While the world awaits a silver bullet, only a prompt integration of basic research, money, and technology will bring it into existence a malaria vaccine within the foreseeable future.
Dr Abhishek Jamwal received his PhD from International Centre for Genetic Engineering and Biotechnology, New Delhi for his work in the field of malaria structural biology. He is currently gaining post-doctoral experience at the Department of Biochemistry, from the University of Oxford under the supervision of Prof. Mathew Higgins. His work entails studying malaria parasite-host interaction dovetailed to vaccine immunogen design.