Engineered flavivirus vaccines control induction of crossreactive infection-enhancing and -neutralizing antibodies. Issue 42 (6th October 2022)

• Record Type: Journal Article
• Authors: Yamanaka, Atsushi; Rattanaamnuaychai, Pimploy; Matsuda, Mami; Suzuki, Ryosuke; Matsuura, Yoshiharu; Tatsumi, Masashi; Konishi, Eiji
• Is Part Of: Vaccine. Volume 40:Issue 42(2022)
• Page Start: 6004
• Page End: 6011
• Publication Date: 2022-10-06
• Subjects: Flavivirus -- DNA vaccine -- Genetic manipulation -- Crossreactivity -- Neutralizing antibody -- Antibody-dependent enhancement; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2022.09.012
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Flavivirus vaccines induce crossreactive neutralizing and enhancing antibodies. Genetically-manipulated DNA vaccines modified crossreactivity against flaviviruses. A manipulation of D87N increased in crossreactive neutralization to flaviviruses. The single amino acid substitution dramatically reduced crossreactive ADE activity. A genetic engineering contributes to develop safe and effective flavivirus vaccine. Abstract: Flaviviruses are important human pathogens because of their global distribution and disease severity. The high structural similarity among flaviviruses induces cross-immunity, with individual flaviviruses exhibiting crossreactive infection-enhancing and/or -neutralizing activities against other flaviviruses. Unlike neutralizing antibodies, enhancing antibodies may increase the risk of disease severity. Vaccine-induced enhancement remains a concern in the development of flavivirus vaccines. Here, we immunized mice with DNA vaccine candidates (pcJEME, pcWNME or pcZIKME) against Japanese encephalitis virus (JEV), West Nile virus (WNV) or Zika virus (ZIKV), respectively, and investigated crossreactive neutralizing and enhancing antibody activities against seven flaviviruses. pcZIKME induced higher cross-neutralization against dengue viruses than against JEV and WNV. Moreover, pcZIKME with a single amino acid substitution (D87N) showed an increase in crossreactive neutralizing activity and a decrease in enhancing activities against other flaviviruses. A similar trend was observed in pcWNME. Engineered antigen might contribute to the development of safe and effective flavivirus vaccines.