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An Aedes–Anopheles Vaccine Candidate Supplemented with BCG Epitopes Against the Aedes and Anopheles Genera to Overcome Hypersensitivity to Mosquito Bites

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Abstract

Background

Skeeter syndrome is a severe local allergic response to mosquito bites that is accompanied by considerable inflammation and, in some cases, a systemic response like fever. People with the syndrome develop serious allergies, ranging from rashes to anaphylaxis or shock. The few available studies on mosquito venom immunotherapy have utilized whole-body preparations and small sample sizes. Still, owing to their little success, vaccination remains a promising alternative as well as a permanent solution for infections like Skeeter’s.

Methods

This study, therefore, illustrated the construction of an epitope-based vaccine candidate against Skeeter Syndrome using established immunoinformatic techniques. We selected three species of mosquitoes, Anopheles melas, Anopheles funestus, and Aedes aegypti, to derive salivary antigens usually found in mosquito bites. Our construct was also supplemented with bacterial epitopes known to elicit a strong TH1 response and suppress TH2 stimulation that is predicted to reduce hypersensitivity against the bites.

Results

A quality factor of 98.9496, instability index of 38.55, aliphatic index of 79.42, solubility of 0.934747, and GRAVY score of -0.02 indicated the structural (tertiary and secondary) stability, thermostability, solubility, and hydrophilicity of the construct, respectively. The designed Aedes–Anopheles vaccine (AAV) candidate was predicted to be flexible and less prone to deformability with an eigenvalue of 1.5911e-9 and perfected the human immune response against Skeeter (hypersensitivity) and many mosquito-associated diseases as we noted the production of 30,000 Th1 cells per mm3 with little (insignificant production of Th2 cells. The designed vaccine also revealed stable interactions with the pattern recognition receptors of the host. The TLR2/vaccine complex interacted with a free energy of − 1069.2 kcal/mol with 26 interactions, whereas the NLRP3/vaccine complex interacted with a free energy of − 1081.2 kcal/mol with 16 molecular interactions.

Conclusion

Although being a pure in-silico study, the in-depth analysis performed herein speaks volumes of the potency of the designed vaccine candidate predicting that the proposition can withstand rigorous in-vitro and in-vivo clinical trials and may proceed to become the first preventative immunotherapy against mosquito bite allergy.

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Data availability

All the data generated in this research work has been included in the manuscript.

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Acknowledgements

The authors are thankful to the Researchers Supporting Project number (RSP2024R462), King Saud University, Riyadh, Saudi Arabia.

Funding

No external funding was received.

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Authors and Affiliations

  1. Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, Lahore, 54590, Punjab, Pakistan

    Muhammad Naveed, Rida Naveed & Sarmad Mahmood

  2. Department of Biotechnology, Quaid-I-Azam University Islamabad, Islamabad, 45320, Pakistan

    Urooj Ali & Muhammad Mustajab Khan

  3. Department of Agriculture, University of Ioannina Arta, 47100, Arta, Greece

    Tariq Aziz

  4. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, 11451, Riyadh, Saudi Arabia

    Metab Alharbi, Thamer H. Albekairi & Abdullah F. Alasmari

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Contributions

Conceptualization, MN, UA, RN, MMK. and TA; methodology, MMK; software, UA; validation, SM, and TA; formal analysis, MN, UA, RN, MMK and TA; investigation, UA and SM; resources, MN; data curation, ASA, MA, and RN; writing—original draft preparation, MA and AAS; writing—review and editing, THA; visualization, TA and RN; supervision, MN and TA; project administration, MMK; funding acquisition, TA.

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Correspondence to Muhammad Naveed or Tariq Aziz.

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Naveed, M., Ali, U., Aziz, T. et al. An Aedes–Anopheles Vaccine Candidate Supplemented with BCG Epitopes Against the Aedes and Anopheles Genera to Overcome Hypersensitivity to Mosquito Bites. Acta Parasit. 69, 483–504 (2024). https://doi.org/10.1007/s11686-023-00771-1

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  • DOI: https://doi.org/10.1007/s11686-023-00771-1

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