Laurent Fischer

Bio: Laurent Fischer is an academic researcher from Merial. The author has contributed to research in topics: DNA vaccination & Vaccination. The author has an hindex of 19, co-authored 32 publications receiving 1067 citations. Previous affiliations of Laurent Fischer include Government of the United States of America.

Sand Fly Salivary Proteins Induce Strong Cellular Immunity in a Natural Reservoir of Visceral Leishmaniasis with Adverse Consequences for Leishmania

Abstract: Immunity to a sand fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-γ at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG2 antibody levels and significant IFN-γ production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-γ and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response.

Equine viral vaccines: the past, present and future

Abstract: The increasing international movement of horses combined with the relaxation of veterinary regulations has resulted in an increased incidence of equine infectious diseases. Vaccination, along with management measures, has become the primary method for the effective control of these diseases. Traditionally modified live and inactivated vaccines have been used and these vaccines have proven to be very successful in preventing disease. However, there are a number of equine infectious diseases for which conventional technology has shown its limitations. The advent of recombinant technology has stimulated the development of second generation vaccines, including gene deleted mutants, live vectored vaccines and DNA vaccines. These vaccines have in common that protective antigens are endogenously processed and presented along the molecules of the MHC I and MHC II complex, resulting in the stimulation of both humoral and cell-mediated immune responses similar to natural infection. The present paper provides a review of the vaccines being employed today against the most important equine viral diseases followed by a summary of new developments that are expected to bring improved vaccines to the market in the foreseeable future.

Current Status of Veterinary Vaccines

Abstract: The major goals of veterinary vaccines are to improve the health and welfare of companion animals, increase production of livestock in a cost-effective manner, and prevent animal-to-human transmission from both domestic animals and wildlife. These diverse aims have led to different approaches to the development of veterinary vaccines from crude but effective whole-pathogen preparations to molecularly defined subunit vaccines, genetically engineered organisms or chimeras, vectored antigen formulations, and naked DNA injections. The final successful outcome of vaccine research and development is the generation of a product that will be available in the marketplace or that will be used in the field to achieve desired outcomes. As detailed in this review, successful veterinary vaccines have been produced against viral, bacterial, protozoal, and multicellular pathogens, which in many ways have led the field in the application and adaptation of novel technologies. These veterinary vaccines have had, and continue to have, a major impact not only on animal health and production but also on human health through increasing safe food supplies and preventing animal-to-human transmission of infectious diseases. The continued interaction between animals and human researchers and health professionals will be of major importance for adapting new technologies, providing animal models of disease, and confronting new and emerging infectious diseases.

Biology of Phlebotomine Sand Flies as Vectors of Disease Agents

Abstract: Phlebotomines are the sole or principal vectors of Leishmania, Bartonella bacilliformis, and some arboviruses. The coevolution of sand flies with Leishmania species of mammals and lizards is considered in relation to the landscape epidemiology of leishmaniasis, a neglected tropical disease. Evolutionary hypotheses are unresolved, so a practical phlebotomine classification is proposed to aid biomedical information retrieval. The vectors of Leishmania are tabulated and new criteria for their incrimination are given. Research on fly-parasite-host interactions, fly saliva, and behavioral ecology is reviewed in relation to parasite manipulation of blood feeding, vaccine targets, and pheromones for lures. Much basic research is based on few transmission cycles, so generalizations should be made with caution. Integrated research and control programs have begun, but improved control of leishmaniasis and nuisance-biting requires greater emphasis on population genetics and transmission modeling. Most leishmaniasis transmission is zoonotic, affecting the poor and tourists in rural and natural areas, and therefore control should be compatible with environmental conservation.

Invited Review Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies

Abstract: A thorough understanding of the transmission mechanism of any infectious agent is crucial to implementing an effective intervention strategy. Here, our current understanding of the mechanisms that Leishmania parasites use to ensure their transmission from sand fly vectors by bite is reviewed. The most important mechanism is the creation of a ‘‘blocked fly’’ resulting from the secretion of promastigote secretory gel (PSG) by the parasites in the anterior midgut. This forces the sand fly to regurgitate PSG before it can bloodfeed, thereby depositing both PSG and infective metacyclic promastigotes in the skin of a mammalian host. Other possible factors in transmission are considered: damage to the stomodeal valve; occurrence of parasites in the salivary glands; and excretion of parasites from the anus of infected sand flies. Differences in the transmission mechanisms employed by parasites in the three subgenera, Leishmania, Viannia and Sauroleishmania are also addressed.

Chikungunya Virus Arthritis in Adult Wild-Type Mice

Abstract: Chikungunya virus is a mosquito-borne arthrogenic alphavirus that has recently reemerged to produce the largest epidemic ever documented for this virus. Here we describe a new adult wild-type mouse model of chikungunya virus arthritis, which recapitulates the self-limiting arthritis, tenosynovitis, and myositis seen in humans. Rheumatic disease was associated with a prolific infiltrate of monocytes, macrophages, and NK cells and the production of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ). Infection with a virus isolate from the recent Reunion Island epidemic induced significantly more mononuclear infiltrates, proinflammatory mediators, and foot swelling than did an Asian isolate from the 1960s. Primary mouse macrophages were shown to be productively infected with chikungunya virus; however, the depletion of macrophages ameliorated rheumatic disease and prolonged the viremia. Only 1 μg of an unadjuvanted, inactivated, whole-virus vaccine derived from the Asian isolate completely protected against viremia and arthritis induced by the Reunion Island isolate, illustrating that protection is not strain specific and that low levels of immunity are sufficient to mediate protection. IFN-α treatment was able to prevent arthritis only if given before infection, suggesting that IFN-α is not a viable therapy. Prior infection with Ross River virus, a related arthrogenic alphavirus, and anti-Ross River virus antibodies protected mice against chikungunya virus disease, suggesting that individuals previously exposed to Ross River virus should be protected from chikungunya virus disease. This new mouse model of chikungunya virus disease thus provides insights into pathogenesis and a simple and convenient system to test potential new interventions.