An octavalent dendrimer of multiple antigenic peptide with a property of pan-coronavirus IgM induction improved clinical signs of feline infectious peritonitis in cats
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 antib...
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Published in | Veterinary vaccine Vol. 3; no. 1; p. 100055 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier B.V
01.03.2024
Elsevier |
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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. |
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AbstractList | 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. |
ArticleNumber | 100055 |
Author | Kuroda, Yudai Okayama, Hiroki Saito, Takashi Sakurai, Masashi Tsukada, Hina Kubo, Masato Tran, Ngo Thuy Bao Obata, Miho Nara, Takuya Weiyin, Hu Suzuki, Chitose Masuda, Kenichi Mitsunaga, Saki Maeda, Ken Shimoda, Hiroshi |
Author_xml | – sequence: 1 givenname: Takuya surname: Nara fullname: Nara, Takuya organization: Emerging Infectious Disease Vaccine Technology Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, RIKEN Baton Zone Program, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan – sequence: 2 givenname: Hiroshi surname: Shimoda fullname: Shimoda, Hiroshi organization: Laboratory of Veterinary Microbiology, Joint Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8515, Japan – sequence: 3 givenname: Chitose surname: Suzuki fullname: Suzuki, Chitose organization: Emerging Infectious Disease Vaccine Technology Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, RIKEN Baton Zone Program, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan – sequence: 4 givenname: Ngo Thuy Bao surname: Tran fullname: Tran, Ngo Thuy Bao organization: Laboratory of Veterinary Microbiology, Joint Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8515, Japan – sequence: 5 givenname: Hina surname: Tsukada fullname: Tsukada, Hina organization: Laboratory of Veterinary Microbiology, Joint Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8515, Japan – sequence: 6 givenname: Hiroki surname: Okayama fullname: Okayama, Hiroki organization: Laboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8515, Japan – sequence: 7 givenname: Hu surname: Weiyin fullname: Weiyin, Hu organization: Laboratory of Veterinary Microbiology, Joint Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8515, Japan – sequence: 8 givenname: Miho surname: Obata fullname: Obata, Miho organization: Laboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8515, Japan – sequence: 9 givenname: Saki surname: Mitsunaga fullname: Mitsunaga, Saki organization: Laboratory of Veterinary Microbiology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8515, Japan – sequence: 10 givenname: Masashi surname: Sakurai fullname: Sakurai, Masashi organization: Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi 753-8515, Japan – sequence: 11 givenname: Yudai orcidid: 0000-0002-7862-6658 surname: Kuroda fullname: Kuroda, Yudai organization: Department of Veterinary Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan – sequence: 12 givenname: Ken surname: Maeda fullname: Maeda, Ken organization: Department of Veterinary Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan – sequence: 13 givenname: Masato surname: Kubo fullname: Kubo, Masato organization: Emerging Infectious Disease Vaccine Technology Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, RIKEN Baton Zone Program, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan – sequence: 14 givenname: Takashi surname: Saito fullname: Saito, Takashi organization: Emerging Infectious Disease Vaccine Technology Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, RIKEN Baton Zone Program, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan – sequence: 15 givenname: Kenichi surname: Masuda fullname: Masuda, Kenichi email: masuda@aacl.co.jp organization: Emerging Infectious Disease Vaccine Technology Laboratory, RIKEN Cluster for Science, Technology and Innovation Hub, RIKEN Baton Zone Program, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan |
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Keywords | Cats Coronaviruses FIP Multiple antigenic peptides Universal vaccine IgM |
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Title | An octavalent dendrimer of multiple antigenic peptide with a property of pan-coronavirus IgM induction improved clinical signs of feline infectious peritonitis in cats |
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