Sterile Protection against Plasmodium knowlesi in Rhesus Monkeys from a Malaria Vaccine: Comparison of Heterologous Prime Boost Strategies

Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost

Adenovirus-5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part B: Safety, Immunogenicity and Protective Efficacy of the CSP Component

Background: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.\ud \ud Methodology/Principal Findings: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1x1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.\ud \ud Significance: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection

Comparative Genomics of the Genomic Region Controlling Resistance to Puccinia Polysora Underw. in Zea Mays L.

Polysora rust (Southern Corn Rust) is a majordisease of maize in tropical and subtropical regioncausing yield loss in excess of 45%. The loci governingresistance (Rpp9, RppQ and RppD) have been mapped to10.01 bins on short arm of maize chromosome 10, whichalso has genes for common rust resistance like Rp1 andRp5. With the publication of maize draft genomicsequence we tried to annotate the region spanning thesegenes using comparative genomic tools. We constructed aphysical map using the various loci and thecorresponding markers, BAC clones and contigs reportedfrom the previous researchers and using MaizeGDB. Thesequence for this region was downloaded frommaizesequence.org. The sequence was scanned for codingregions using GENSCAN and the CDS and peptidesobtained along with the whole sequence (in bits of 1 MB)was subjected to BLAST analysis in NCBI-nBLAST,NCBI-pBLAST, COGE-BLAST and MaizeGDB BLAST.The region when located on a physical map, had all theloci governing Polysora rust resistance in a overlappingposition and was around 3 MB size. Two loci RppQ andRppD covered large portion of the 3MB region whereasRpp9 was 82769 bp long. The BLAST results indicatedthe similarity of the region to many loci responsible fordisease resistance like PR protein, Serine/threoninekinase protein, rust resistance protein (rp3-1), receptorkinases and zein cluster. The region shared homologywith rice, sorghum and brachypodium grass and wefound some orthologs having NB-LRR domain. Hencefrom this analysis it could be concluded that the region isresponsible for disease resistance and host many othergenes linked with resistance to various diseases

Inter comparison of wave height observations from buoy and altimeter with numerical prediction

1347-1351An inter-comparison exercise has been carried out between altimeter derived significant wave height with buoy measurements and numerical prediction. Measurements during the year 2004 have been taken from the buoys located in the Arabian Sea and Bay of Bengal. The statistics of variation between these observations has been studied at each buoy locations with the special emphasis to explore the applicability of altimeter measurements and numerical model prediction.</span