Immune Responses After Malaria Infection and Next Generation Malaria Vaccine

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines Against Tropical and Other Infectious Diseases".

Deadline for manuscript submissions: closed (31 January 2026) | Viewed by 985

Special Issue Editor


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Guest Editor
Yale School of Medicine, New Haven, CT, USA
Interests: Plasmodium; host–vector interaction; antimalaria vaccine; vector biology

Special Issue Information

Dear Colleagues,

Malaria continues to pose a significant threat to global health. Current vaccines provide only suboptimal and waning protection, highlighting the urgent need for a deeper understanding of immunity following infection and immunization. Such fundamental knowledge is essential for the development of enhanced strategies that could eradicate malaria.

The success of mRNA vaccines in combating COVID-19 has provided novel insights into the development of vaccines against infectious diseases. The exploration of novel vaccine modalities, including mRNA technology, is crucial for addressing the persistent challenge of malaria. Additionally, the identification of new antigens that prevent transmission, targeting both the various stages of Plasmodium and its mosquito vector, should be prioritized as part of next-generation vaccine strategies.

To obtain a comprehensive understanding of the immune response to malaria and the latest advances in vaccine development, this Special Issue will focus on recent scientific progress and technological innovations in the field. We invite you to contribute original research, observations, or review articles that explore the following areas: 1) Immune responses during or after malaria infection; 2) Immune development and protection following vaccination; and 3) Advances in the development of vaccines, including antigen discovery and innovative delivery strategies.

We look forward to receiving your contributions, which will help shape the future of malaria vaccine research.

Dr. Yu-Min Chuang
Guest Editor

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Keywords

  • humoral immune response
  • cellular immune response
  • malaria
  • antimalaria vaccine
  • Plasmodium

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Published Papers (1 paper)

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Research

24 pages, 4384 KB  
Article
Cellular Immune Response and T Cell Epitope Mapping of Plasmodium falciparum Chimeric Vaccine Candidate GMZ2.6c and Its Components (MSP-3, GLURP and Pfs48/45) in Individuals Naturally Exposed to Malaria in Brazilian Amazon
by Barbara de Oliveira Baptista, Isabela Ferreira Soares, Hugo Amorim dos Santos de Souza, Jenifer Peixoto de Barros, Evelyn Kety Pratt Riccio, Rodrigo Medeiros Martorano, Rodrigo Nunes Rodrigues-da-Silva, Linda Eva Amoah, Susheel Kumar Singh, Michael Theisen, Josué da Costa Lima-Junior, Paulo Renato Rivas Totino, Cláudio Tadeu Daniel-Ribeiro and Lilian Rose Pratt-Riccio
Vaccines 2026, 14(5), 423; https://doi.org/10.3390/vaccines14050423 - 8 May 2026
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Abstract
Background/Objectives: The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that contains a fragment of the sexual stage Pfs48/45-6c protein genetically fused to GMZ2, which is an asexual stage vaccine construct consisting of conserved domains of Glutamate-Rich Protein (GLURP) and [...] Read more.
Background/Objectives: The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that contains a fragment of the sexual stage Pfs48/45-6c protein genetically fused to GMZ2, which is an asexual stage vaccine construct consisting of conserved domains of Glutamate-Rich Protein (GLURP) and Merozoite Surface Protein-3 (MSP-3). Previous studies showed that GMZ2.6c is widely recognized by antibodies from individuals living in endemic areas of Brazil and that levels of anti-GMZ2.6c increase with malaria exposure and may contribute to immunity against the parasite. As cell-mediated responses are crucial for parasite control and protection, identifying antigens that elicit antigen-specific T cell recall in naturally exposed populations is the key to vaccine development. This study aimed to evaluate the cellular immune response against GMZ2.6c and its components (MSP-3, GLURP, and Pfs48/45) and to identify promiscuous T cell epitopes in individuals exposed to malaria in the Brazilian Amazon, considering the impact of active P. falciparum infection on antigen-specific T cell recall. Methods: This study was carried out using peripheral blood mononuclear cells (PBMCs) from individuals with active P. falciparum infection (PFI) and non-infected individuals exposed to malaria (NI) from Cruzeiro do Sul and Mâncio Lima, Acre State, and Guajará, Amazonas State. The PBMCs were stimulated with GMZ2.6c and its components, and cellular activation, CD4+ and CD8+ memory T cell subsets, and cytokine production were evaluated by flow cytometry. IFN-γ-secreting T cells were quantified by ELISpot using predicted T cell epitopes. Results: The individuals infected by P. falciparum displayed more CD8+ T cell activation in response to MSP-3 and Pfs48/45 and an increase in CD4+ TCM cells and a reduction in CD4+ TEM cells following stimulation with Pfs48/45 and GMZ2.6c. The PBMCs from both groups showed elevated production of IL-6 and TNF after stimulation with GMZ2.6c, MSP-3, and Pfs48/45, but only the non-infected individuals had high levels of IL-10. T cell epitope prediction identified sequences within MSP-3, GLURP, and Pfs48/45 that elicited IFN-γ responses in both the non-infected and P. falciparum-infected individuals. Conclusions: Individuals exhibit cellular immune responses to MSP-3 and Pfs48/45 that are recalled following GMZ2.6c stimulation. P. falciparum infection may modulate immune response, inducing a prominent pro-inflammatory response. Conversely, in the absence of the parasite, the individuals displayed balanced Th1/Th2 cytokine production. Several promiscuous T cell epitopes were able to recall IFN-γ responses. Further studies are needed to fully ascertain the potential of GMZ2.6c as a protective candidate vaccine against malaria. Full article
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