**4. Conclusions**

WNV remains a significant threat to humans, equids, and birds in many parts of the world, as demonstrated by the worrisome increase of cases reported in the E.U. in recent years. An accumulated number of 285 human cases and 31 deaths were reported to the European Centre for Disease Prevention and Control (ECDC) in 2020 [43]. This increase is favored, among other reasons, by the introduction or imposition of new lineages, the increase in temperature that can favor the colonization of new regions by mosquito vectors competent for their transmission, and the globalization of trade and the transport of people and animals. All this makes it necessary to have effective and inexpensive vaccines for immediate use.

As has been detailed, the technologies to produce vaccines are already available and have proved to be safe and protective in the few clinical trials conducted. In this regard, and even though clinical trials are difficult to establish, vaccination in restricted regions where outbreaks appear could help not only to combat the spread of infection but also to ge<sup>t</sup> a better idea of the performance of vaccines in terms of protection, the durability of immunity, etc. In any case, some issues should be improved and properly addressed to facilitate its introduction into the market. Among them are a solid demonstration of the induction of a long-lasting immunity, preferably after a single immunization, the production and validation of marked candidates, the exclusion of the possibility of inducting a putative ADE phenomenon, its safety in elderly and immunocompromised people, and the optimization of their production to reduce their costs. To solve these issues, a joint effort of the different agents involved (pharmaceutical companies, governments, international institutions, and non-governmental organizations) to establish a common fund for its development, clinical trials implementation, and the establishment of adequate vaccination strategies would be desirable.

**Funding:** This research was funded by Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, (INIA), gran<sup>t</sup> number E-RTA2017-00003-C02-01, and Comunidad Autónoma de Madrid, gran<sup>t</sup> number S2018/BAA-4370-ZOOVIR (PLATESA2-CM).

**Conflicts of Interest:** The author declares no conflict of interest. The funders had no role in the manuscript.
