YF17D‐based vaccines – standing on the shoulders of a giant

• Published in: European journal of immunology Vol. 54; no. 5; pp. e2250133 - n/a
• Main Authors: Sanchez‐Felipe, Lorena, Alpizar, Yeranddy A., Ma, Ji, Coelmont, Lotte, Dallmeier, Kai
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-05-2024
• Subjects: Animals; Cell-mediated immunity; Emerging infectious diseases; Encephalitis; Hepatitis; HIV; Human immunodeficiency virus; Humans; Humoral immunity; Immunization; Immunogenicity; Live‐attenuated recombinant vaccines; Parasitic diseases; Severe acute respiratory syndrome coronavirus 2; Systems vaccinology; Therapeutic applications; Therapeutic vaccines; Tropical diseases; Vaccination - methods; Vaccine efficacy; Vaccines; Vaccines, Attenuated - immunology; Yellow fever; Yellow Fever - immunology; Yellow Fever - prevention & control; Yellow fever vaccine (YF17D); Yellow Fever Vaccine - immunology; Yellow fever virus - immunology; Systems vaccinology; Emerging infectious diseases; Therapeutic vaccines; Live‐attenuated recombinant vaccines; Yellow fever vaccine (YF17D)
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.202250133

Summary
Live‐attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single‐dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS‐CoV‐2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D‐based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D‐based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness.
Graphical : Live‐attenuated yellow fever vaccine (YF17D) has emerged as platform to develop prophylactic and therapeutic vaccines against infectious diseases and cancer. In this review, we summarize the unique polyfunctional immunity endowed by original YF17D, and the progress and challenges of recombinant YF17D‐based vaccines for unmet medical needs and pandemic preparedness.