Globally, malaria continues to cause substantial morbidity and mortality rates, and especially in sub-Saharan Africa the insect-borne disease still affects millions every year. Currently, there are excellent medical therapies and multiple effective preventative measures readily available for addressing the major health burden of malaria. However, to ultimately achieve sustainable control and eventual eradication of malaria, the development of an effective malaria vaccine is vitally important. This overview highlights the current progress in anti-malarial vaccine research and product development, addressing the challenges we face today and exploring potential future directions. This field is crucial for public health, as it aims to combat one of humanity’s oldest and most persistent threats.
The Importance of Malaria Vaccines
Plasmodium-based malaria is an illness transmitted to humans through the bite of infected female Anopheles mosquitoes. These mosquitoes carry the Plasmodium parasites, which invade red blood cells and cause the symptoms associated with malaria. Typically, symptoms start with flu-like signs but can rapidly develop into a serious life-threatening illness. Disturbingly, malaria remains a significant burden to humanity, both in terms of human suffering and economic impact, and there is an ever-growing need for a vaccine that is both effective and affordable.
Vaccines offer a more robust preventive strategy than other measures, potentially generating lifetime immunity, thus sparing the need for repeated treatments. Insecticide-treated nets are an essential component of malaria control, as are indoor residual spraying with insecticide, and antimalarials. But a vaccine would complement these strategies by offering increased and more sustainable general protection.
Milestones in Malaria Vaccine Development
1. RTS, S/AS01 Vaccine: A Breakthrough
Mosquirix, also known as RTS, S/AS01, is the most advanced malaria vaccine developed to combat Plasmodium falciparum, the deadliest malaria parasite. Created by GlaxoSmithKline (GSK) in collaboration with the PATH Malaria Vaccine Initiative, Mosquirix represents a significant step forward in the fight against malaria.
- Licensure and Rollout: In 2015, RTS, S/AS01 became the first malaria vaccine with regulatory approval. By 2021, the World Health Organization (WHO) recommended it for use in malaria-endemic parts of Africa as well as in the Greater Mekong Subregion. Since approval, the vaccine has demonstrated the ability to reduce malaria incidence in young children, but its efficacy is modest in comparison to effective vaccines for other diseases.
- Vaccine Mechanism: comes to grips with the parasite, blocking the entry of P falciparum parasites into the liver, where they ultimately hide and infect the bloodstream, despite it being low in efficacy. It was, however, a breakthrough.
2. Current and Next-Generation Vaccines
Ongoing research is focused on improving existing vaccines and developing new candidates:
- RTS, S/AS02: This is the same as the RTS, S vaccine used in the earlier trials. It has now been modified to have even better efficacy and durability.
- PfSPZ Vaccine: The PfSPZ vaccine is a whole, attenuated Plasmodium falciparum sporozoite vaccine that was created by Sanaria. In clinical trials, it has demonstrated robust efficacy against malaria infections.
- VAR2CSA-Based Vaccines: These vaccines target the VAR2CSA protein present on the surface of Plasmodium falciparum-infected red blood cells and block the parasite’s ability to adhere to the placental tissue, protecting pregnant women and their infants.
- Multi-Stage and Multi-Component Vaccines: some of the current vaccines under trial are either multi-stage against multiple stages of the parasite’s lifecycle or multi-component through combining different antigens against multiple pathogens that cause malaria for enhanced protection. These include vaccines against the liver stage, blood stage, and the mosquito stage of the parasite.
Challenges in Malaria Vaccine Development
Despite the progress, several challenges persist in the development of effective malaria vaccines:
1. Complexity of the Malaria Parasite
The true problem with a vaccine seems to lie in the fact that Plasmodium has various lifecycle stages, each with different antigenic profiles, so, likely, one wouldn’t be entirely effective in protecting against all stages of the parasite’s life cycle.
- Antigenic Variation: The genotypic diversity of plasmodium parasites causes antigenic variation. Since a vaccine targeting one strain may be less efficacious against others, antigenic variation may also affect vaccine efficacy.
- Immune evasion: Evading immunity of its host: the malaria parasite has ways of escaping or rendering ineffective the host’s immunity, such as constant changes to its surface proteins, to keep out of the view of immune detection.Vaccine development: These factors underlie the difficulty in creating effective vaccines for the malaria parasite.
2. Safety and Efficacy
When developing a malaria vaccine, it’s important that it is safe and protects as many people as possible, such as the most susceptible and others at risk, including pregnant women, infants, children, older individuals, and travelers. This is particularly difficult, however, for several reasons.
- Long-Term Protection: RTS, S/AS01 (and most other malaria vaccines currently under development) confers only partial and transient protection; work continues to enhance the duration and potency of vaccines.
- Safety: vaccines must also be carefully tested so as not to cause harm. Careful monitoring of the safety profile is necessary, especially when vaccines are being provided in populations with higher rates of malaria transmission.
3. Manufacturing and Distribution
The production and distribution of malaria vaccines pose logistical and economic challenges:
Production Costs: It is expensive to develop and manufacture vaccines. Malaria vaccines will not be accessible in low-resource settings if their production costs remain high.
Cold Chain Requirements: While some vaccines tolerate storage above 4 degrees Celsius, the World Health Organization (WHO) does not endorse this practice. There have been instances where vaccines were stored at temperatures as high as 37 degrees Celsius, compromising their efficacy. In regions with inadequate infrastructure, maintaining the proper temperature for storing and transporting vaccines presents significant challenges.
Future Directions in Malaria Vaccine Research
To overcome the challenges and achieve malaria elimination, several strategies are being explored:
1. Advancing Vaccine Platforms
Innovative vaccine platforms are being designed to boost efficacy and overcome shortcomings in current vaccines:
- mRNA vaccines– The rapid development of mRNA vaccines against COVID-19 paves the way to apply this vaccine platform to malaria and offers opportunities for a rapid update to popularise new vaccines against new strains.
- Vaccines based on Virus-Like Particle (VLP) that mimic the malaria parasite to provoke a strong immune response are another example. VLP-based vaccines remain a subject of research to further enhance their efficacy and safety profile.
2. Combination Approaches
Combining different vaccine candidates or integrating vaccines with other interventions could enhance overall protection:
- Vaccine-drug combinations: engineering vaccines that target mix with antimalarial drugs to provide synergistic effects to simultaneously prevent and treat.
- Combining vaccination with control measures such as insecticide-treated nets and indoor residual spraying (Integrated Interventions) could increase overall efficacy. Another area of research focuses on eliminating and eradicating (NOTE) malaria.
3. Global Collaboration and Investment
Collaboration among researchers, governments, and organizations is essential for advancing malaria vaccine development:
- Public-Private Partnerships: the cooperation between public institutions, public agencies, and private companies can allow the production and distribution of vaccines.
- Increased backing: continuing investments in malaria research will be necessary if we are to persist and finally find the answers to workable vaccines
Vaccine research and development against malaria has evolved tremendously with the development of candidate vaccines such as the RTS, and S/AS01 vaccine. Nonetheless, there are still formidable challenges ahead, including the number and complexity of the antigens involved in the malaria parasite, the need for high safety and efficacy, biosafety, manufacturing and distribution, and more.
