The frequency, magnitude, and longevity of natural antibody responses against nine P. vivax vaccine candidate proteins

Malaria is a significant public health threat, causing about 241 million cases worldwide in 2020. Although Plasmodium falciparum is reported to be the most common malaria parasite in Africa, P. vivax is the predominant parasite in most countries in America and Asia Pacific. Critical illnesses caused by P.vivax are no more considered rare events.

Background

The WHO has recommended the widespread use of the RTS,S vaccine against P. falciparum. However, this vaccine is not cross-protective against P. vivax. Therefore, a highly effective vaccine against P. vivax is required urgently.

A durable and specific immune response against antigens important for the survival of the parasite can be induced by an ideal malaria blood-stage vaccine. Parasite-specific antibodies can disrupt the interactions between cognate host receptors required for RBC invasion and parasite ligands, thereby providing immunity against blood-stage malaria.

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Previous studies in Papua New Guinea children identified several antigens as vaccine candidates, such as Duffy binding protein region II (DBPII), Pv41, Pv12, RBP2b, RBP1a, PVX_081550, and erythrocyte binding protein (EBP). Recent research indicated antibodies to PvRBP2b to protect against clinical malaria in Thailand and Brazil.

The study of antibody dynamics after and during naturally acquired acute infection can help in the identification of serological markers of exposure to the pathogen. It can also help to understand the longevity and magnitude of natural humoral immunity to vaccine-candidate antigens. This, in turn, can help in the development of vaccines.

Characterization of the natural IgG responses to the antigens in other malaria-transmission settings can provide information on how their natural immunogenicity may impact vaccine responses. Moreover, identifying antigen targets that lead to durable and robust antibody responses can help develop vaccines on candidate antigens that benefit from the boosting due to natural pathogen exposure.

A new study in PLOS Neglected Tropical Diseases aimed to evaluate the magnitude, longevity, and prevalence of naturally acquired IgG antibody responses against 9 P. vivax vaccine candidate antigens in patients with acute vivax malaria and were followed up for 180 days.

About the study

The study involved the enrolment of 47 participants with uncomplicated, acute P. vivax malaria between May 2013 and August 2014. The recruitment of participants took place from four farming settlements in northwestern Brazil. Tentative species identification and parasitemia were determined by examining thick blood smears and confirmed by real-time PCR.

Collection of venous blood samples took place into heparinized tubes at the time of admission as well as post-admission days 30, 60, and 180. This was followed by the expression of P. vivax recombinant proteins and their coupling. Finally, the multiplex immunoassay was carried out.

Study findings

The results indicated that 37 individuals completed the 30-day follow-up, 19 completed the 60-day follow-up, and 8 completed the 180-day follow-up. Strong and positive correlations of IgG reactivity were observed between PVX_081550, PvGAMA, Pv41, and Pv12 at baseline. A strong correlation for IgG reactivity against PVX_081550 and Pv41 was observed across all four-time points. However, strong and positive correlations were observed between PvEBP and Pv41 at day 60, between Pv12 and PVX_081550 and Pv41 at day 180, as well as between PvEBP and PvGAMA at day 180.

All infected participants were reported to be seropositive for all antigens except PvRBP1a by day 30. 100% of participants were seropositive for Pv41 and 90 to 91% for PvGAMA on days 30 and 60. More than 70% of individuals were reported to be seropositive against the individual antigens PvRBP2b, PvGAMA, and Pv41.

A decrease in specific IgG post-infection was observed for each of the 8 P. vivax antigens. Antibodies against Pv41, PvRBP2b, PVX_81550, and Pv12 were observed to have a slower decay rate than antibodies PvMSP3a, PvDBP-FL, PvEBP, and PvGAMA. Antibodies to PVX_081550 were observed to have the highest half-life followed by PvRBP2b and Pv12. However, antibodies against PvGAMA, PvMSP3a, and PvDBP-FL were observed to have shorter half-lives.

Conclusion

Therefore, the current study demonstrates that several recently identified P. vivax vaccine candidate antigens can be targeted for natural antibody response during and after acute vivax malaria. Robust IgG responses have been reported against PvGAMA and Pv41. Estimation of seropositivity indicated PvRBP2b, PvGAMA, and Pv41, while assessment of half-lives indicated Pv12, PvRBP2b, and PVX_081550 to lead to the most durable IgG responses. However, further studies are required to determine whether such antibodies protect against clinical malaria in the community.

Limitations

The current study has certain limitations. First, the study lacked pre-infection baseline samples. Second, only a small number of participants participated in the 180-day follow-up. Third, the 30 days follow-up is mostly a couple of weeks after the peak antibody response took place for most individuals. Fourth, different subclass reactivity of IgG was not determined. Fifth, the seropositivity thresholds might not be able to indicate background cross-reactivity among malaria-naïve individuals. Finally, the study could not determine the functional significance of the antibody response to the antigens.

Written by

Suchandrima Bhowmik

Suchandrima has a Bachelor of Science (B.Sc.) degree in Microbiology and a Master of Science (M.Sc.) degree in Microbiology from the University of Calcutta, India. The study of health and diseases was always very important to her. In addition to Microbiology, she also gained extensive knowledge in Biochemistry, Immunology, Medical Microbiology, Metabolism, and Biotechnology as part of her master's degree.