Abstract:
Background: The GMZ2.6c malaria vaccine candidate is a multi-stage Plasmodium falciparum chimeric protein which
contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP
and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.6c in
humans. Considering that circulating parasites can be genetically distinct in different malaria-endemic areas and that
host genetic factors can influence the immune response to vaccine antigens, it is important to verify the antigenicity,
immunogenicity and the possibility of associated protection in individuals living in malaria-endemic areas with diferent epidemiological scenarios. Herein, the profile of antibody response against GMZ2.6c and its components (MSP-3,
GLURP and Pfs48/45) in residents of the Brazilian Amazon naturally exposed to malaria, in areas with different levels of
transmission, was evaluated.
Methods: This study was performed using serum samples from 352 individuals from Cruzeiro do Sul and Mâncio
Lima, in the state of Acre, and Guajará, in the state of Amazonas. Specifc IgG, IgM, IgA and IgE antibodies and IgG
subclasses were detected by Enzyme-Linked Immunosorbent Assay.
Results: The results showed that GMZ2.6c protein was widely recognized by naturally acquired antibodies from
individuals of the Brazilian endemic areas with different levels of transmission. The higher prevalence of individuals
with antibodies against GMZ2.6c when compared to its individual components may suggest an additive effect of
GLURP, MSP-3, and Pfs48/45 when inserted in a same construct. Furthermore, naturally malaria-exposed individuals
predominantly had IgG1 and IgG3 cytophilic anti-GMZ2.6c antibodies, an important fact considering that the acquisition of anti-malaria protective immunity results from a delicate balance between cytophilic/non-cytophilic antibodies.
Interestingly, anti-GMZ2.6c antibodies seem to increase with exposure to malaria infection and may contribute to
parasite immunity.
Conclusions: The data showed that GMZ2.6c protein is widely recognized by naturally acquired antibodies from
individuals living in malaria-endemic areas in Brazil and that these may contribute to parasite immunity. These data
highlight the importance of GMZ2.6c as a candidate for an anti-malarial vaccine.