Genetic diversity of Plasmodium falciparum AMA-1 antigen from the Northeast Indian state of Tripura and comparison with global sequences: implications for vaccine development

• Published in: Malaria Journal
• Main Authors: Tulika Nirmolia, Md. Atique Ahmed, Vinayagam Sathishkumar, Nilanju P. Sarma, Dibya R. Bhattacharyya, Pradyumna K. Mohapatra, Devendra Bansal, Praveen K. Bharti, Rakesh Sehgal, Jagadish Mahanta, Ali A. Sultan, Kanwar Narain, Saurav J. Patgiri
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2022
• Subjects: Apical Membrane Antigen 1 (AMA-1); Plasmodium falciparum; Genetic diversity; Tripura; Northeast India; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic; Indian
• Online Access: https://doi.org/10.1186/s12936-022-04081-1; https://doaj.org/article/d417478bf36748afa71336aa1860736f

Abstract Background Malaria continues to be a major public health problem in the Northeastern part of India despite the implementation of vector control measures and changes in drug policies. To develop successful vaccines against malaria, it is important to assess the diversity of vaccine candidate antigens in field isolates. This study was done to assess the diversity of Plasmodium falciparum AMA-1 vaccine candidate antigen in a malaria-endemic region of Tripura in Northeast India and compare it with previously reported global isolates with a view to assess the feasibility of developing a universal vaccine based on this antigen. Methods Patients with fever and malaria-like illness were screened for malaria and P. falciparum positive cases were recruited for the current study. The diversity of PfAMA-1 vaccine candidate antigen was evaluated by nested PCR and RFLP. A selected number of samples were sequenced using the Sanger technique. Results Among 56 P. falciparum positive isolates, Pfama-1 was successfully amplified in 75% (n = 42) isolates. Allele frequencies of PfAMA-1 antigen were 16.6% (n = 7) for 3D7 allele and 33.3% (n = 14) in both K1 and HB3 alleles. DNA sequencing revealed 13 haplotypes in the Pfama-1 gene including three unique haplotypes not reported earlier. No unique amino-acid substitutions were found. Global analysis with 2761 sequences revealed 435 haplotypes with a very complex network composition and few clusters. Nucleotide diversity for Tripura (0.02582 ± 0.00160) showed concordance with South-East Asian isolates while recombination parameter (Rm = 8) was lower than previous reports from India. Population genetic structure showed moderate differentiation. Conclusions Besides documenting all previously reported allelic forms of the vaccine candidate PfAMA-1 antigen of P. falciparum, new haplotypes not reported earlier, were found in Tripura. Neutrality tests indicate that the Pfama-1 population in Tripura is under balancing selection. This is consistent with global patterns. However, the ...