Two malaria vaccines were recommended by the World Health Organization (WHO) after three decades of research: RTS,S and R21. The vaccines were recommended in 2021 and 2023, respectively. Both target Plasmodium falciparum and reduce hospitalizations and severe malaria in children, but neither vaccine is available in Brazil. However, even if they were available, they would have addressed only a small proportion of malaria cases in the country because P vivax is the predominant species in Brazil, unlike in Africa, where these vaccines were developed. Therefore, Brazil needs a vaccine specifically suited to its malaria burden.

While P falciparum infects mature red blood cells that can be cultured in the laboratory, P vivax, which accounts for 80% of malaria cases in Brazil, infects only reticulocytes, which are immature red blood cells that are much more difficult to maintain in culture. For decades, this characteristic has limited vaccine development against P vivax. However, it also opened an unexpected path toward a different vaccine strategy.

In 2018, a study published in Nature Medicine showed that P vivax-infected reticulocytes express human leukocyte antigen (HLA) class I molecules on their surface, making them detectable by CD8+ T cells. These cells can recognize and destroy infected reticulocytes, suggesting a previously underappreciated role for T-cell responses against blood-stage Plasmodium. The findings were promising but incomplete. Researchers still need to identify which parasite antigens are present and determine whether a vaccine could induce this response.

Recently, the same researchers addressed this question. Using immunopeptidomics of P vivax-infected reticulocytes, a study led by Caroline F. Junqueira, PhD, from the Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil, and the Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland, identified 453 unique parasite-derived peptides mapped to 166 proteins. Of these, 75 antigens are housekeeping proteins expressed constitutively across multiple stages of the parasite life cycle and are highly conserved among Plasmodium species.

Identical peptides were presented by individuals with different HLA alleles, including the HLA-E allele, a nonclassical HLA class I gene. T-cell responses were validated using samples from Brazilian patients infected with P vivax, patients in Mali infected with P falciparum, and nonhuman primates. Two antigens induced protective CD8+ T cell-mediated immunity in mouse models.

Speaking with Medscape’s Portuguese edition, Daniel Y. Bargieri, PhD, from the Department of Parasitology, Institute of Biomedical Sciences at the University of São Paulo in São Paulo, Brazil, said, “To our knowledge, there are no vaccines based on a CD8+ T-cell response. The others were developed to induce antibody production.”

The malaria vaccine candidate UniMav uses a different vaccination approach. It could potentially target multiple stages of the parasite life cycle and protect against both P vivax and P falciparum because the identified antigens are highly conserved between the two species.

“We will now conduct toxicity studies so that we can submit the required documentation to Anvisa,” said Luna B. de Lacerda , PhD, a researcher and a co-author of the study. The researchers expect to submit a clinical development dossier to the agency in 2027. If the vaccine is approved, the first human volunteer could be vaccinated approximately 18 months after approval.

Two Candidates

UniMav is not the only Brazilian vaccine candidate that targets P vivax. Another candidate, Vivaxin, is approaching human testing. The vaccine is being developed under the coordination of co-principal investigator Irene da Silva Soares, PhD, professor and head of the Department of Clinical and Toxicological Analysis at the University of São Paulo’s School of Pharmaceutical Sciences, in partnership with the Center of Technology in Vaccines (CT-Vacinas) of the Federal University of Minas Gerais (UFMG).

The vaccine candidate is designed to combine the three known P vivax circumsporozoite protein (PvCSP) alleles into a single molecule. The strategy aims to induce neutralizing antibodies and T-cell responses that can block the parasite before it reaches the liver.

“Our target is the PvCSP on the parasite’s surface. Studies indicate that it remains in human skin for several hours before reaching the liver, and the vaccine should neutralize it before that occurs,” Soares said.

In mouse models, the formulation induced recognition of all three protein variants and provided sterile protection in some animals. The trial, which will be conducted at UFMG’s Hospital das Clínicas in Belo Horizonte, will include 48 adults with no history of malaria and follow a randomized, double-blind, placebo-controlled design.

The development of an effective vaccine against P vivax is challenging. The parasite can remain in the liver as hypnozoites and reactivate weeks or months after the initial infection, causing relapses even after treatment in the acute phase. Asymptomatic infections are also common and can sustain transmission without individuals knowing that they are infected.

Species diagnosis can also be difficult. Mixed infections with P falciparum and P vivax may go undetected in the absence of molecular testing. “Early diagnosis and correct species identification are essential. Tests such as PCR [polymerase chain reaction] are important for detecting mixed or asymptomatic infections that conventional microscopy may fail to identify,” Soares said. “It will be difficult to meet elimination targets without an effective vaccine, even with strict mosquito control measures and appropriate treatment of patients,” she added.

The situation could become more complex. A study led by a researcher at the University of São Paulo School of Public Health, published in Scientific Reports in 2025, identified Brazil as a potential route for the introduction of Anopheles stephensi, a mosquito native to Asia that has become an invasive species in 14 countries, mainly in Africa, where it has already caused urban malaria outbreaks.

Unlike A darlingi, the main malaria vector in Brazil and one associated primarily with forested areas, A stephensi lays its eggs in containers of standing water and can adapt to urban environments. The study projects that by 2100, 56% of the world’s population could live in areas with a climate suitable for mosquitoes. According to this study, maritime trade is the main potential route for the introduction of this vector into Brazil because systematic port surveillance for the vector is not in place. If A stephensi is established, malaria could spread beyond its predominantly Amazonian distribution in Brazil.

Indigenous Territories

In April 2026, Brazil became the first country in the world to administer tafenoquine to children. The drug was administered as a single dose to pediatric patients in the Yanomami community to eliminate hepatic hypnozoites and prevent relapses caused by P vivax.

Brazil’s Ministry of Health registered 33,300 cases of malaria in the Yanomami Indigenous Territory in 2024, a figure that exceeded the local population of 27,100 individuals.

Nearly half (44%) of the cases occurred in children aged 9 years or younger. The number of reported cases can exceed the population because the same individual may be diagnosed with malaria multiple times during a year as a result of relapse. Malaria-related deaths in the territory fell by 80.8% in 2025, compared with January 2023, when the government declared a public health emergency in the region.

Clarinha Glock is a Brazilian journalist who holds a master’s degree in education and works as a regular contributor and writer for portugues.medscape.com. She has contributed to newspapers and magazines, covering health and medicine and their intersection with human rights.

This story was translated from Medscape’s Portuguese edition.