Malaria vaccine

The World Health Organization has granted approval for a new vaccine that scientists contend will be a transformative development in the battle against malaria, a disease that claims the lives of half a million individuals in Africa annually. The R21/Matrix vaccine, created by Oxford University in collaboration with the Serum Institute of India, has been shown in trials to reduce malaria by up to 75 percent. It can be produced inexpensively and on a large scale. The Conversation Weekly recently interviewed Adrian Hill, the chief investigator and director of the Jenner Institute at the University of Oxford, regarding this groundbreaking vaccine. The following are edited excerpts from the podcast.

What makes the R21/Matrix vaccine a game-changer?

We are observing roughly 75 percent efficacy by measuring the decrease in malaria cases over the course of a year. The previous best vaccine was approximately 50 percent effective over a year and even less so over three years.

While this is a significant improvement, it is not the primary improvement. The major difference is the ability to manufacture the vaccine on a scale that is necessary to safeguard the majority of children in Africa who require a malaria vaccine.

Approximately 40 million children are born each year in malaria-endemic regions of Africa who would benefit from a vaccine. Our vaccine is a four-dose regimen administered over 14 months, necessitating roughly 160 million doses. We can accomplish this.

Our manufacturing and commercial partner, the Serum Institute of India, can produce hundreds of millions of doses of this vaccine each year, whereas the previous vaccine could only be produced at a scale of six million doses per year from 2023 to 2026, according to Unicef reports.

The third significant benefit of this vaccine lies in its affordability. We were fully cognizant of the fact that a vaccine priced at US$100 would not be feasible for international organizations involved in procuring and disseminating vaccines in economically disadvantaged nations.

Consequently, the current pricing structure is designed to be flexible, with the cost per dose set at US$5 for high-volume orders, subject to variation based on the scale of the purchase.

The challenges encountered in the development of a malaria vaccine can be attributed to the ambitious goal of producing millions of doses annually from 2023 to 2026, as indicated by reports from Unicef.

Malaria is not classified as a virus or bacterium; rather, it is categorized as a protozoan parasite, significantly larger than a typical virus. This distinction is evident in the number of genes present in each organism, with Covid possessing 13 genes while malaria boasts approximately 5,500 genes. This substantial genetic disparity contributes to the intricate nature of malaria.

The parasite assumes various forms, the initial of which are introduced into the skin by mosquitoes and promptly migrate to the liver. There, they undergo a week-long period of rapid multiplication before entering the bloodstream. Notably, these parasites exhibit marked dissimilarities throughout these distinct stages. Furthermore, their growth rate is astonishing, multiplying exponentially at a rate of tenfold every 48 hours.

Once the parasite density reaches a significantly high level, one's health will deteriorate severely. In unfortunate cases, fatality may occur, often resulting from cerebral symptoms, a coma, or severe anemia, all of which are caused by the rupture of red blood cells by the parasites.

Furthermore, there exists an additional stage in which the parasite undergoes a transformation, enabling it to be transmitted to another individual through the mosquito's subsequent bite, thus perpetuating the life cycle.

Hence, the complexity of infectious pathogens is exemplified by these intricate processes.

Malaria, in particular, undergoes four distinct life cycles, each with its own unique characteristics. Developing an effective vaccine for any of these cycles would disrupt the transmission cycle, which has been the primary objective of our endeavors.

Our research has been focused on targeting the sporozoites, the form of the malaria parasite that is inoculated into the skin by mosquitoes. Our aim is to intercept the parasite before it reaches the liver and progresses through its life cycle. Fortunately, this stage of infection is asymptomatic until the parasite enters the bloodstream and begins to multiply within red blood cells. Therefore, the sporozoite presents a natural target for intervention before rapid multiplication occurs.

Regarding past efforts to develop a malaria vaccine, early attempts involved using the entire microbe, similar to Edward Jenner's use of the whole virus to inoculate against smallpox. Later, bacterial vaccines were developed by microbiologist Louis Pasteur. In 1943, a trial of a whole malaria parasite vaccine candidate in New York yielded zero efficacy, which discouraged further attempts for some time. It was not until the 1980s, when gene sequencing of the parasite became possible, that new vaccination candidates emerged. Within a decade, 5,000 candidates were identified, as researchers hoped that the genes they sequenced might lead to a malaria vaccine. However, the vast majority of these candidates ultimately proved unsuccessful.

Why are vaccines targeting whole parasites not effective against malaria? The reason lies in the fact that simply getting infected once by malaria does not provide protection against subsequent infections.

In the regions of Africa where our vaccines are tested for malaria, some children experience up to eight episodes within a span of three or four months. The initial infection causes significant illness, and three weeks later they suffer from a second bout, and so on. Natural immunity does not develop until an individual has experienced numerous different infections. This is why adults are generally protected against malaria and do not become severely ill.

In endemic areas, it is the young children who have never been infected before that are most vulnerable to malaria-related deaths. They may succumb to their first infection at the age of one, or they may have had one or two episodes, but these were insufficient to provide sterilizing immunity.

Malaria has existed for millions of years, not only in humans but also in our pre-human ancestors. It is an incredibly cunning parasite that has evolved various mechanisms to evade the immune system.

When attempting to develop a vaccine, we encounter the parasite's ability to circumvent our efforts. It is only when antibody levels reach exceptionally high levels, ones that the parasite has not encountered before and has not adapted against, that the vaccine becomes effective.

Is it conceivable that malaria will be completely eradicated in the future? Malaria holds a prominent position among the diseases that we aspire to eliminate. Although it is unlikely to occur within the next five or ten years, it is plausible to anticipate its eradication within a timeframe of approximately fifteen years. Therefore, setting the year 2040 as a reasonable target seems appropriate.

It is important to note that the current efforts involving the implementation of bed nets, spraying, and medication should not be halted. However, it is worth acknowledging the existence of a novel tool that possesses the potential to provide greater individual protection compared to the aforementioned methods.