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

Malaria Journal

Rakesh Sehgal¹  Ali A. Sultan²  Devendra Bansal³  Praveen K. Bharti⁴  Dibya R. Bhattacharyya⁵  Saurav J. Patgiri⁵  Kanwar Narain⁵  Md. Atique Ahmed⁵  Vinayagam Sathishkumar⁵  Pradyumna K. Mohapatra⁵  Tulika Nirmolia⁵  Jagadish Mahanta⁵  Nilanju P. Sarma⁶ 

[1] Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, 160012, Chandigarh, Punjab, India;Department of Microbiology and Immunology, Weill Cornell Medicine - Qatar, Cornell University, Doha, Qatar;Department of Microbiology and Immunology, Weill Cornell Medicine - Qatar, Cornell University, Doha, Qatar;Ministry of Public Health, Doha, Qatar;ICMR - National Institute for Research in Tribal Health, 482003, Jabalpur, Madhya Pradesh, India;ICMR - Regional Medical Research Centre, North East Region, 786001, Dibrugarh, Assam, India;ICMR - Regional Medical Research Centre, North East Region, 786001, Dibrugarh, Assam, India;SRL Reference Laboratory, 400060, Mumbai, India;

关键词: Apical Membrane Antigen 1 (AMA-1);    Plasmodium falciparum;    Genetic diversity;    Tripura;    Northeast India;   

DOI  :  10.1186/s12936-022-04081-1

来源: Springer

【 摘 要 】

BackgroundMalaria 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.MethodsPatients 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.ResultsAmong 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.ConclusionsBesides 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 high haplotype diversity observed in the global Pfama-1 network analysis indicates that designing a universal vaccine based on this antigen may be difficult. This information adds to the existing database of genetic diversity of field isolates of P. falciparum and may be helpful in the development of more effective vaccines against the parasite.

【 授权许可】

CC BY