Kevin Lucien, Sylvie Laumond, Marine Minier, Cameron P. Simmons, Nadège Rossi, Myrielle Dupont-Rouzeyrol, Olivia O’Connor, Nicolas Pocquet, Tristan Derycke, Frédéric Touzain, Sylvie Russet, Elodie Chalus, Heather A. Flores, David J. Hooker, Florie Cheilan, Catherine Inizan, Jordan Tutagata, Morgane Pol, Johanna M. Duyvestyn, Daniela da Silva Gonçalves, Etiene C. Pacidônio, Dominique Girault, Entomologie médicale [Nouméa, Nouvelle-Calédonie] (URE-EM), Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Dengue et Arbovirose (URE-DA), Monash University [Melbourne], Réseau International des Instituts Pasteur (RIIP), Centre hospitalier territorial Gaston-Bourret [Nouméa], Mairie de Nouméa [Nouvelle-Calédonie], Direction des Affaires sanitaires et sociales de la Nouvelle-Calédonie [Nouméa] (DASS [Nouméa]), Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), University of Oxford [Oxford], This work was supported by the Institut Pasteur de Nouvelle-Calédonie, the New Caledonia government, the Nouméa City Council , the University of Monash, and the Fonds de coopération économique, sociale et culturelle pour le Pacifique (grant number UO 209DRP0457)., and We are grateful to the Direction des Affaires Sanitaires et Sociales de la Nouvelle-Calédonie, the Mairie de Nouméa, the Institut Pasteur de Nouvelle-Calédonie, and the University of Monash for their contribution to the implementation of this project in Noumea, New Caledonia. We would like to thank all the staff from Centre de Don du Sang et Service de Transfusion Sanguine from Centre Hospitalier Territorial Gaston Bourret, Nouvelle-Calédonie, for their involvement and support. We warmly thank the Clinical Research Department of the Centre for Translational Research at Institut Pasteur in Paris for their support in ethic procedures. DENV isolates were obtained from the World Reference Center for Emerging Viruses and Arboviruses. Roy Hall kindly provided the 4G2 antibody used in TCID50 experiments. We would like to thank Jaana Wenham and Mason Mason for technical assistance. We would like to thank Sosiasi Kilama and Sophie Hagen for technical support. We deeply thank Marc Jouan, Vincent Richard, and Jean-Paul Grangeon for their unshakeable support in the implementation of the project in Noumea, New Caledonia.
Background Biological control programs involving Wolbachia-infected Aedes aegypti are currently deployed in different epidemiological settings. New Caledonia (NC) is an ideal location for the implementation and evaluation of such a strategy as the only proven vector for dengue virus (DENV) is Ae. aegypti and dengue outbreaks frequency and severity are increasing. We report the generation of a NC Wolbachia-infected Ae. aegypti strain and the results of experiments to assess the vector competence and fitness of this strain for future implementation as a disease control strategy in Noumea, NC. Methods/principal findings The NC Wolbachia strain (NC-wMel) was obtained by backcrossing Australian AUS-wMel females with New Caledonian Wild-Type (NC-WT) males. Blocking of DENV, chikungunya (CHIKV), and Zika (ZIKV) viruses were evaluated via mosquito oral feeding experiments and intrathoracic DENV challenge. Significant reduction in infection rates were observed for NC-wMel Ae. aegypti compared to WT Ae. aegypti. No transmission was observed for NC-wMel Ae. aegypti. Maternal transmission, cytoplasmic incompatibility, fertility, fecundity, wing length, and insecticide resistance were also assessed in laboratory experiments. Ae. aegypti NC-wMel showed complete cytoplasmic incompatibility and a strong maternal transmission. Ae. aegypti NC-wMel fitness seemed to be reduced compared to NC-WT Ae. aegypti and AUS-wMel Ae. aegypti regarding fertility and fecundity. However further experiments are required to assess it accurately. Conclusions/significance Our results demonstrated that the NC-wMel Ae. aegypti strain is a strong inhibitor of DENV, CHIKV, and ZIKV infection and prevents transmission of infectious viral particles in mosquito saliva. Furthermore, our NC-wMel Ae. aegypti strain induces reproductive cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, supporting field-releases in Noumea, NC., Author summary Dengue represents a risk for almost half of the world’s population, especially throughout the tropics. In New Caledonia, dengue outbreaks have become more frequent in the past decade along with the recent circulation of chikungunya and Zika viruses. The opportunity to use the biocontrol method involving the release of Wolbachia-infected Ae. aegypti mosquitoes has been investigated as an alternative solution to the traditional control methods, like elimination of larval habitats and pyrethroid insecticide application to kill adults, which are becoming insufficient. A local strain of Ae. aegypti carrying Wolbachia (NC-wMel) has been generated and tested to evaluate its pathogen blocking capacity for the four dengue virus serotypes as well as chikungunya and Zika viruses. The fitness of NC-wMel strain has also been assessed to estimate its ability to compete with the wild-type strain in the field. Noumea city, where a third of the population of New Caledonia resides, has been chosen as the first site to implement the method in New Caledonia. As Ae. aegypti is the only proven vector in New Caledonia, we expect a significant impact on dengue outbreaks occurring in Noumea as soon as a high frequency of NC-wMel is established in the population.