Comparative assessment of transmission-blocking vaccine candidates against Plasmodium falciparum.

Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species, and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform.

Stress dependent infection cost of the human malaria agent Plasmodium falciparum on its natural vector Anopheles coluzzii.

Unraveling selective forces that shape vector-parasite interactions has critical implications for malaria control. However, it remains unclear whether Plasmodium infection induces a fitness cost to their natural mosquito vectors. Moreover, environmental conditions are known to affect infection outcome and may impact the effect of infection on mosquito fitness. We investigated in the laboratory the effects of exposition to and infection by field isolates of Plasmodium falciparum on fecundity and survival of a major vector in the field, Anopheles coluzzii under different conditions of access to sugar resources after blood feeding. The results evidenced fitness costs induced by exposition and infection. When sugar was available after blood meal, infected and exposed mosquitoes had either reduced or equal to survival to unexposed mosquitoes while fecundity was either increased or decreased depending on the blood donor. Under strong nutritional stress, survival was reduced for exposed and infected mosquitoes in all assays. We therefore provide here evidence of an environmental-dependant reduced survival in mosquitoes exposed to infection in a natural and one of the most important parasite-mosquito species associations for human malaria transmission.

Anopheles funestus (Diptera: Culicidae) in a humid savannah area of western Burkina Faso: bionomics, insecticide resistance status, and role in malaria transmission.

An entomological survey was carried out in three humid savannah sites of western Burkina Faso (Bama, Lena, and Soumousso) to (1) update the taxonomy of the Anopheles funestus Giles group, (2) examine the role of each species in malaria transmission, (3) characterize the insecticide resistance status of this malaria vector, and (4) determine the distribution of An. funestus chromosomal forms in these areas. Polymerase chain reaction identification of the members showed the occurrence of An. leesoni Evans in Lena and An. rivulorum-like in Soumousso in addition to An. funestus s.s. Malaria transmission was ensured mainly by An. funestus s.s. both in Soumousso and Lena and by An. gambiae s.s. Giles in Bama, the rice-growing area. The insecticide resistance status performed only on An. funestus indicated that this mosquito was susceptible to pyrethroids irrespective of the study area, but it was resistant to dieldrin. Furthermore, the occurrence of the two chromosomal forms of An. funestus, namely, Kiribina and Folonzo, seemed to follow ecological setups where Kiribina predominated in the irrigated area and Folonzo was more frequent in classic savannah. This study revealed that the problematic of An. funestus taxonomy was closer to that of An. gambiae requiring more structured studies to understand its genetic ecology.

[Malaria vectors: from the field to genetics. Research in Africa]. / Vecteurs de paludisme: du terrain à la génétique moléculaire. Recherches en Afrique.

Only about 60 Anopheline species transmit malaria among more than 3,000 mosquito species recorded in the world. In Africa, the major vectors are Anopheles gambiae,An. arabiensis, An. funestus, An. nili and An. moucheti. They all belong to species complexes or groups of closely related species that are very difficult to set apart on morphological grounds, but which may have highly variable behaviours and vectorial capacities. Understanding this complexity is of major importance in vector control programs or for implementing any public health intervention program such as drugs or vaccine trials. Among the seven species of the complex,Anopheles gambiaes.s. shows a huge chromosomal polymorphism related to adaptation to specific natural or anthropic environments, from equatorial forested Africa to dry sahelian areas. Recent studies conducted in West and Central Africa suggest an incipient speciation into 2 molecular forms provisionally called M and S. A similar evolutionary phenomenon is observed in An. funestus, in which sympatric populations carrying specific chromosomal paracentric inversions showed restricted gene flow. Distribution of species from An. nili group and An. moucheti complex is restricted to more humid regions of Africa. However in some areas these species play the major role in malaria transmission. Comprehensive knowledge of transmission cycles and of behavioural and underlying genetic heterogeneities that exist within and among natural vector populations will thus benefit the whole area of malaria control and epidemiology. Molecular and genetic studies, as well as in depth monitoring of vector biology, have been recently facilitated by advances in functional and comparative genomics, including recent publication of the nearly complete genome sequence of An. gambiae. Challenge for the next years is to answer to the very simple question: why is an insect a vector?

Population structure of the malaria vector Anopheles funestus in Senegal based on microsatellite and cytogenetic data.

The study of chromosomal inversions distribution within natural Anopheles funestus populations from West Africa revealed high levels of genetic structuring. In Burkina Faso, this was interpreted as evidence for incipient speciation, and two chromosomal forms were described, namely 'Folonzo' and 'Kiribina'. Assignation of field collected specimens to one chromosomal form depends upon application of an algorithm based on chromosomal inversions. We assessed relevance and applicability of this algorithm on An. funestus populations from Senegal, where both forms occur. Furthermore, we estimated the level of genetic differentiation between populations using microsatellite loci spread over the whole genome. Significant genetic differentiation was revealed between geographical populations of An. funestus, and the pattern observed suggested isolation by distance. Chromosomal heterogeneity was not detected by microsatellite markers. Thus, although incipient speciation could not be ruled out by our data, our results suggest that differential environmental selection pressure acting on inversions should be considered a major factor in shaping their distribution in wild An. funestus populations.

A microsatellite map of the African human malaria vector Anopheles funestus.

Microsatellite markers and chromosomal inversion polymorphisms are useful genetic markers for determining population structure in Anopheline mosquitoes. In Anopheles funestus (2N = 6), only chromosome arms 2R, 3R, and 3L are known to carry polymorphic inversions. The physical location of microsatellite markers with respect to polymorphic inversions is potentially important information for interpreting population genetic structure, yet none of the available marker sets have been physically mapped in this species. Accordingly, we mapped 32 polymorphic A. funestus microsatellite markers to the polytene chromosomes using fluorescent in situ hybridization (FISH) and identified 16 markers outside of known polymorphic inversions. Here we provide an integrated polytene chromosome map for A. funestus that includes the breakpoints of all known polymorphic inversions as well as the physical locations of microsatellite loci developed to date. Based on this map, we suggest a standard set of 16 polymorphic microsatellite markers that are distributed evenly across the chromosome complement, occur predominantly outside of inversions, and amplify reliably. Adoption of this set by researchers working in different regions of Africa will facilitate metapopulation analyses of this primary malaria vector.

[Systematics and biology of Anopheles vectors of Plasmodium in Africa, recent data]. / Systématique et biologie des anophèles vecteurs de Plasmodium en Afrique, données récentes.

Renewed interest in research on Plasmodium vectors in Africa and development of genetic and molecular biology techniques has been spearheaded by the WHO and the PAL+ program of the French research ministry. New findings have led to a better understanding of the systematics and biology of the main vector groups. The purpose of this article is to describe the newest data on the Anopheles gambiae complex and the M and S forms of An. gambiae s.s., on species in the An. funestus group and genetic polymorphism of An. funestus, on the two probable species in the An. moucheti complex, and on An. mascarenesis.