Immunogenicity & safety of a single dose of live-attenuated Japanese encephalitis vaccine SA 14-14-2 in adults

Background & objectives: Japanese encephalitis (JE) caused by mosquito-borne Flavivirus is one of the leading causes of viral encephalitis in Asia. Control strategies include vector control and human vaccination. Due to lack of immunization programmes in endemic regions, there are still high mortality and morbidity. A live-attenuated SA 14-14-2 JE vaccine (LAJEV) has been licensed and used in Asian countries, including India. We report the assessment of immunogenicity and safety of the vaccine in adults during the first mass adult vaccination campaign carried out in Assam, India. Methods: One thousand and seventy five adults (aged ≥15 yr) who received LAJEV were monitored for adverse events following immunization for one year. The safety assessment of vaccinated population was evaluated till 28 days and at 6 and 12 months. Blood samples collected from the enrolled participants were tested by plaque reduction neutralization test (PRNT 50 ) to assess the neutralizing antibody titres (NATs) before vaccination and 28 days, six and 12 months post-vaccination (PV). Results: Among the 1075 vaccinated individuals, four reported minor adverse effects from 30 min to 28 days PV. Based on the pre-vaccination NAT, the study participants were categorized as seronegative, moderately seropositive and strongly seropositive. Nearly 85.5 per cent of JE seronegative participants seroconverted by 28 days PV. The geometric mean titre (GMT) in all the three groups increased by 28 days and decreased by six and 12 months PV. Nearly 60 per cent of the moderately positive individuals exhibited four-fold rise in GMT, 28 days PV. Almost 95.5 per cent of the participants in the study population remained seroprotected at the end of 12 months PV. Interpretation & conclusions: This study on immunogenicity and safety of LAJEV in adults showed that a single dose of the live-attenuated vaccine was safe and induced protective immunity to both JE seronegative and naturally seropositive adults. Further study is required to find out long term protective efficacy of this vaccine

Molecular characterization of Plasmodium falciparum in Arunachal Pradesh from Northeast India based on merozoite surface protein 1 & glutamate-rich protein

Background & objectives: Northeast (NE) India is one of the high endemic regions for malaria with a preponderance of Plasmodium falciparum, resulting in high morbidity and mortality. The P. falciparum parasite of this region showed high polymorphism in drug-resistant molecular biomarkers. However, there is a paucity of information related to merozoite surface protein 1 (msp-1) and glutamate-rich protein (glurp) which have been extensively studied in various parts of the world. The present study was, therefore, aimed at investigating the genetic diversity of P. falciparum based on msp-1 and glurp in Arunachal Pradesh, a State in NE India. Methods: Two hundred and forty nine patients with fever were screened for malaria, of whom 75 were positive for P. falciparum. Blood samples were collected from each microscopically confirmed patient. The DNA was extracted; nested polymerase chain reaction and sequencing were performed to study the genetic diversity of msp-1 (block 2) and glurp. Results: The block 2 of msp-1 gene was found to be highly polymorphic, and overall allelic distribution showed that RO33 was the dominant allele (63%), followed by MAD20 (29%) and K1 (8%) alleles. However, an extensive diversity (9 alleles and 4 genotypes) and 6-10 repeat regions exclusively of R2 type were observed in glurp. Interpretation & conclusions: The P. falciparum population of NE India was diverse which might be responsible for higher plasticity leading to the survival of the parasite and in turn to the higher endemicity of falciparum malaria of this region

Map of India showing the study site.

<p>Map of India showing the study site.</p

Distribution of allelic family and size variations of vaccine candidate genes in Indian <i>P</i>. <i>falciparum</i> isolates.

<p>Distribution of allelic family and size variations of vaccine candidate genes in Indian <i>P</i>. <i>falciparum</i> isolates.</p

Frequency distribution of different allelic variations of <i>P</i>. <i>falciparum msp1</i>, <i>msp2</i> and <i>glurp</i> genes in Indian isolates.

<p>Frequency distribution of different allelic variations of <i>P</i>. <i>falciparum msp1</i>, <i>msp2</i> and <i>glurp</i> genes in Indian isolates.</p

Type of repeats sequence with limited polymorphism of <i>P</i>. <i>falciparum glurp</i> gene in the Indian isolates.

<p>Type of repeats sequence with limited polymorphism of <i>P</i>. <i>falciparum glurp</i> gene in the Indian isolates.</p

Nucleotide diversity test of neutrality and rate of recombination test of vaccine candidate genes in Indian <i>P</i>. <i>falciparum</i> isolates.

<p>Nucleotide diversity test of neutrality and rate of recombination test of vaccine candidate genes in Indian <i>P</i>. <i>falciparum</i> isolates.</p

Global population structure of <i>P</i>. <i>falciparum msp1</i>, <i>msp2</i> and <i>csp</i> gene.

<p>A minimal spanning tree (MST) generated using Bio Numerics software version 7.6.1 showing the relationship from worldwide isolates. Each circle represents and individual haplotype and the size of the circle is proportional to the number of isolates belonging to that haplotypes. The line connecting the circle is branch length.</p