In Silico Analyzing 37 kDa Salivary Protein D7 and Discovering Vaccine Candidate and Diagnostic Epitopes to Develop a Transmission-blocking Multi-epitope Vector Vaccine Against Aedes Species (A. aegypti and A. albopictus) Transmitting Several Arboviral Pathogens
Abstract
Aedes mosquitoes, primarily Aedes aegypti and Aedes albopictus, are significant vectors of arboviral diseases, including dengue, chikungunya, Zika, and yellow fever. With expanding geographical distributions due to climate change and urbanization, these species increasingly threaten public health. Current vector control strategies rely heavily on insecticides, which face challenges due to increased resistance. An alternative approach involves developing transmission-blocking vaccines targeting mosquito vector proteins rather than individual pathogens. This study performed an in-silico analysis of the 37 kDa salivary protein D7, a highly conserved and abundantly secreted protein in Aedes saliva, to identify potential vaccine and diagnostic epitopes. Through sequence comparison, structural modeling, and immunoinformatics approaches, B-cell, MHC-I, and MHC-II epitopes with high antigenicity, non-allergenicity, and non-toxicity were predicted. Selected epitopes were incorporated into multi-epitope vaccine constructs against A. aegypti and A. albopictus vectors, which were subsequently modeled, validated, and simulated to induce IgM, IgG, and IFN-g. The present study's findings suggest that the 37 kDa salivary protein D7 is a promising candidate for a transmission-blocking vector vaccine targeting Aedes mosquitoes, offering a novel strategy for controlling mosquito-borne diseases. Further experimental validation is necessary to confirm the immunogenicity and protective potential of the identified epitopes.
Keywords
References
- A. Nebbak, L. Almeras, P. Parola, I. Bitam, Mosquito vectors (Diptera: Culicidae) and mosquito-borne diseases in North Africa, Insects 13 (10) (2022) 962.
- S. Liu, X. Xia, E. Calvo, Z. H. Zhou, Native structure of mosquito salivary protein uncovers domains relevant to pathogen transmission, Nature Communications 14 (2023) 899.
- E. Gavor, Y. K. Choong, Y. Liu, J. Pompon, E. E. Ooi, Y. K. Mok, H. Liu, R. M. Kini, J. Sivaraman, Identification of Aedes aegypti salivary gland proteins interacting with human immune receptor proteins, PLoS Neglected Tropical Diseases 16 (9) (2022) e0010743.
- D. C. Rinker, R. J. Pitts, L. J. Zwiebel, Disease vectors in the era of next generation sequencing, Genome Biology 17 (1) (2016) 95.
- C. H. Coelho, R. Rappuoli, P. J. Hotez, P. E. Duffy, Transmission-blocking vaccines for malaria: time to talk about vaccine introduction, Trends in Parasitology 35 (7) (2019) 483–486.
- S. Buezo Montero, P. Gabrieli, A. Poinsignon, B. Z. H. Zamble, F. Lombardo, F. Remoue, B. Arcà, Human IgG responses to the Aedes albopictus 34k2 salivary protein: Analyses in Reunion Island and Bolivia confirm its suitability as marker of host exposure to the tiger mosquito, Parasites and Vectors 15 (1) (2022) 260.
- B. R. Egid, M. Coulibaly, S. K. Dadzie, B. Kamgang, P. J. McCall, L. Sedda, K. H. Toe, A. L. Wilson, Review of the ecology and behaviour of Aedes aegypti and Aedes albopictus in Western Africa and implications for vector control, Current Research in Parasitology and Vector-Borne Diseases 2 (2022) 100074.
- L. Braack, A. P. Gouveia de Almeida, A. J. Cornel, R. Swanepoel, C. De Jager, Mosquito-borne arboviruses of African origin: review of key viruses and vectors, Parasites and Vectors 11 (2018) 29.
- S. J. Ryan, C. J. Carlson, E. A. Mordecai, L. R. Johnson, Global expansion and redistribution of Aedes-borne virus transmission risk with climate change, PLoS Neglected Tropical Diseases 13 (3) (2019) e0007213.
- N. Vasilakis, J. Cardosa, K. A. Hanley, E. C. Holmes, S. C. Weaver, Fever from the forest: prospects for the continued emergence of sylvatic dengue virus and its impact on public health, Nature Reviews Microbiology 9 (7) (2011) 532–541.