Research update: Malaria vaccine development

By Naveed Saleh, MD, MS | Fact-checked by Barbara Bekiesz
Published December 14, 2023

Key Takeaways

  • Endemic cases of malaria in the US are on the rise, although the number of such cases still remains low.

  • Despite decades of research, malaria vaccines have proven difficult to develop.

  • RTS,S/AS01,and R21/Matrix-M have been shown to be partially effective in fighting malaria in clinical trials.

Malaria was officially eradicated from the US in early 1950, after the establishment of the Office of Malaria Control in War Areas, which later became the CDC.

Better sanitation, improved medical care, technological advances, and increased use of insecticides resulted in the interruption of malaria transmission. Despite elimination of endemic transmission of the parasite, however, Anopheles vectors remain in the US.

Although there is effective treatment for malaria, a vaccine could prevent infection in the first place. However, the discovery of a highly effective vaccine has proven elusive.

Malaria in the states

The mean number of malaria cases has risen during the past few decades, as reported by the CDC. A malaria review article published in Current Tropical Medicine Reports notes that, overall, 1,773 malaria cases per year are reported on average, with 98.8% imported from outside the US (especially Sub-Saharan Africa).[]

In June 2023, the Florida Department of Health issued a statewide mosquito-borne illness advisory after there were four confirmed local cases of malaria in Sarasota County.[]

An October 2023 update posted by the CDC saw this number rise to 10 total—seven in Florida and one case each in Arkansas, Texas, and Maryland, with “no evidence to suggest that any of the cases are related,” per the CDC.[] 

The authors of the malaria review article summarized the various factors that may contribute to malaria’s persistence. “Despite the lack of recent autochthonous cases in the USA,” they wrote, “multiple risk factors suggest that local malaria outbreaks in the USA will continue to pose a public health threat due to large numbers of international travelers from endemic areas, multiple Anopheles spp. capable of transmitting the parasite, and unsatisfactory vector-borne disease outbreak preparedness."

"Climate conditions and recent changes in travel patterns will influence malaria across the globe."

Authors, Current Tropical Medicine Reports

According to the UN, climate change may increase the transmission of malaria. As discussed in the UN Chronicle:[]

“Climate change would, perhaps, increase the epidemic potential of malaria in tropical countries currently susceptible to the disease. Increasing temperatures and global travel have the potential to reintroduce or increase transmission of malaria in tropical and temperate countries that have either eliminated or controlled transmission. Such countries would be prone to epidemics, since surveillance and preparedness for malaria control may not be as intense as when malaria was a major public health problem in these countries. It is in this context that surveillance and preparedness need to be emphasized, not compromised.” 

A long road to the first vaccine

The 60-year journey to a malaria vaccine is recounted in Tropical Medicine and Health.[]

The development of a malaria vaccine has long been hindered by the genetic diversity and complicated life cycle of Plasmodium (the malaria parasite), along with a lack of sterile immunity in malaria.

The development of a modern vaccine stemmed from efforts in the 1960s involving primates, rodents, and humans, testing irradiated sporozoites. Continuing efforts yielded the first malaria vaccine in 2021—which was also the first parasite vaccine—which was then approved for widespread use: RTS,S/AS01. The WHO recommended its broader use in at-risk children living in African countries and other areas where P. falciparum has high or moderate transmission. 

In phase 2 and 3 clinical trials in children, the RTS vaccine demonstrated about 56% effectiveness over 1 year and, in the longer phase 3 trial, 36% effectiveness over 4 years. The  safety profile was acceptable. As yet, the long-term effects of the vaccine on child health and its impact on targeted communities remain to be elucidated.

The authors of the review article in Tropical Medicine and Health shared this perspective on the vaccine’s role: “[A]lthough RTS,S vaccine has been approved for wider use in endemic African countries and elsewhere, it might not be sufficient as a stand-alone measure for effective malaria control. In order to achieve malaria elimination, it is wiser to consider the vaccine as an addition to current measures rather than as a replacement for them. A protocol to guide countries on how to incorporate the vaccine into their control measures is being developed.”

A second vaccine

The R21/Matrix-M vaccine, an improved version of the RTS,S vaccine, was studied in a double-blind phase 1/2b randomized controlled trial in children living in Burkina Faso.[]

The children’s ages ranged between 5 and 17 months. The efficacy of the R21/Matrix-M vaccine reached the WHO-specified efficacy goal of 75% or more. Efficacy of 77% was observed in children receiving four doses of the vaccine, which is the same dosing needed to fight off infection with the RTS,S vaccine.[] Neither vaccine requires sub-zero storage, and both have long shelf lives, which makes them especially useful in countries where malaria is endemic.

The investigators for the Burkina Faso study expressed optimism regarding this vaccine. “Delivered seasonally, the R21/Matrix-M vaccine continues to show an acceptable safety profile in the second year of follow-up and following a fourth dose,” they concluded. “Together with maintained high efficacy, these findings suggest that this malaria vaccine and vaccination strategy could have a substantial impact in areas of highly seasonal malaria transmission in Africa.”

The R21/Matrix-M vaccine is now in phase 3 trials, involving 4,800 children living in east and west Africa.

What this means for you

Although the chances of being infected with locally acquired malaria in the US are low, cases are on the rise. Climate change could further exacerbate the problem. Currently, two partially effective anti-malaria vaccines have been discovered, although these interventions may not suffice as standalone measures in the battle against malaria.

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