1. An octavalent dendrimer of multiple antigenic peptide with a property of pan-coronavirus IgM induction improved clinical signs of feline infectious peritonitis in cats
- Author
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Takuya Nara, Hiroshi Shimoda, Chitose Suzuki, Ngo Thuy Bao Tran, Hina Tsukada, Hiroki Okayama, Hu Weiyin, Miho Obata, Saki Mitsunaga, Masashi Sakurai, Yudai Kuroda, Ken Maeda, Masato Kubo, Takashi Saito, and Kenichi Masuda
- Subjects
Multiple antigenic peptides ,Coronaviruses ,Universal vaccine ,IgM ,FIP ,Cats ,Veterinary medicine ,SF600-1100 - Abstract
Feline infectious peritonitis (FIP) is a lethal disease caused by a pathogenic coronavirus, feline infectious peritonitis virus (FIPV), in cats. Effective vaccines have been unsuccessful due to the frequent mutation of FIPV and antibody-dependent enhancement (ADE) caused by vaccine-induced IgG antibodies (Abs). This study examined the induction of pan-coronavirus IgM Ab in mice and its ameliorating effects in feline FIP using CoV-mMAP8, an octavalent dendrimer composed of multiple antigenic peptides. The 11-amino acid peptide (SAIEDLLFNKV) was designed as the highly conserved region of the fusion peptide at the N-terminus of S2’ subunit of the spike protein found in human and animal coronaviruses and was then conjugated to an octavalent dendrimer to form CoV-mMAP8. After a total of three injections of CoV-mMAP8 into Balb/c mice with α-galactosylceramide (α-GC) co-administered in the second injection, serum titers of IgM Abs increased against the peptide, recombinant spike proteins of SARS-CoV-2 and MERS-CoV, and crude viral antigens of canine coronavirus, porcine endemic diarrhea virus, and FIPV. In contrast, serum titers of IgG Abs did not significantly increase against any antigens. When CoV-mMAP8 was injected into three cats experimentally infected with FIPV, hyperthermia was improved within seven days after the injection with ameliorating inflammatory markers such as the platelet-to-lymphocyte ratio and the systemic immune-inflammatory index. One cat that showed recurrent hyperthermia received an additional injection of CoV-mMAP8, and clinical improvement was observed again. Postmortem examinations confirmed chronic lesions of FIP in all the cats, providing evidence that FIPV had been successfully infected and treated with CoV-mMAP8 in all the cats. Based on the induction of pan-coronavirus IgM Abs in mice and ameliorating effects in FIP of cats, it is assumed that CoV-mMAP8 has the potential to overcome the challenges posed by variants and ADE in FIPV. The mutational compatibility of CoV-mMAP8 can make it a viable universal vaccine for various coronaviruses beyond FIPV.
- Published
- 2024
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