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A circular mRNA vaccine prototype producing VFLIP-X spike confers a broad neutralization of SARS-CoV-2 variants by mouse sera.
Seephetdee, Chotiwat; Bhukhai, Kanit; Buasri, Nattawut; Leelukkanaveera, Puttipatch; Lerdwattanasombat, Pat; Manopwisedjaroen, Suwimon; Phueakphud, Nut; Kuhaudomlarp, Sakonwan; Olmedillas, Eduardo; Saphire, Erica Ollmann; Thitithanyanont, Arunee; Hongeng, Suradej; Wongtrakoongate, Patompon.
  • Seephetdee C; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: chotiwat.sep@student.mahidol.ac.th.
  • Bhukhai K; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: kanit.bhu@mahidol.ac.th.
  • Buasri N; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: nattawut.bua@alumni.mahidol.ac.th.
  • Leelukkanaveera P; International Program of Bioinnovation, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: puttipatch.lee@student.mahidol.edu.
  • Lerdwattanasombat P; International Program of Biomedical Science, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: pat.ler@student.mahidol.edu.
  • Manopwisedjaroen S; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: swiboonut@gmail.com.
  • Phueakphud N; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: nut_phu@hotmail.com.
  • Kuhaudomlarp S; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Center for Excellence in Protein and Enzyme Technology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: sakonwan.kuh@mahidol.ac.th.
  • Olmedillas E; La Jolla Institute for Immunology, La Jolla, CA, 92037, USA. Electronic address: eolmedillas@lji.org.
  • Saphire EO; La Jolla Institute for Immunology, La Jolla, CA, 92037, USA. Electronic address: erica@lji.org.
  • Thitithanyanont A; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: arunee.thi@mahidol.ac.th.
  • Hongeng S; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand. Electronic address: suradej.hon@mahidol.ac.th.
  • Wongtrakoongate P; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: patompon.won@mahidol.ac.th.
Antiviral Res ; 204: 105370, 2022 08.
Article in English | MEDLINE | ID: covidwho-1906743
ABSTRACT
Next-generation COVID-19 vaccines are critical due to the ongoing evolution of SARS-CoV-2 virus and rapid waning duration of the neutralizing antibody response against current vaccines. The mRNA vaccines mRNA-1273 and BNT162b2 were developed using linear transcripts encoding the prefusion-stabilized trimers (S-2P) of the wildtype spike, which have shown a reduced neutralizing activity against the variants of concern B.1.617.2 and B.1.1.529. Recently, a new version of spike trimer, termed VFLIP (five (V) prolines, Flexibly-Linked, Inter-Protomer disulfide) was developed. Based on the original amino acid sequence of the wildtype spike, VFLIP was genetically engineered by using five proline substitutions, a flexible cleavage site amino acid linker, and an inter-protomer disulfide bond. It has been suggested to possess native-like glycosylation, and greater pre-fusion trimeric stability as opposed to S-2P. Here, we report that the spike protein VFLIP-X, containing six rationally substituted amino acids to reflect emerging variants (K417N, L452R, T478K, E484K, N501Y and D614G), offers a promising candidate for a next-generation SARS-CoV-2 vaccine. Mice immunized by a circular mRNA (circRNA) vaccine prototype producing VFLIP-X had detectable neutralizing antibody titers for up to 7 weeks post-boost against SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs). In addition, a balance in TH1 and TH2 responses was achieved by immunization with VFLIP-X. Our results indicate that the VFLIP-X delivered by circRNA induces humoral and cellular immune responses, as well as broad neutralizing activity against SARS-CoV-2 variants.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Circular / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / MRNA Vaccines Topics: Vaccines / Variants Limits: Animals Language: English Journal: Antiviral Res Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Circular / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / MRNA Vaccines Topics: Vaccines / Variants Limits: Animals Language: English Journal: Antiviral Res Year: 2022 Document Type: Article