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A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants.
Pishesha, Novalia; Harmand, Thibault J; Rothlauf, Paul W; Praest, Patrique; Alexander, Ryan K; van den Doel, Renate; Liebeskind, Mariel J; Vakaki, Maria A; McCaul, Nicholas; Wijne, Charlotte; Verhaar, Elisha; Pinney, William; Heston, Hailey; Bloyet, Louis-Marie; Pontelli, Marjorie Cornejo; Ilagan, Ma Xenia G; Jan Lebbink, Robert; Buchser, William J; Wiertz, Emmanuel J H J; Whelan, Sean P J; Ploegh, Hidde L.
  • Pishesha N; Society of Fellows, Harvard University, Cambridge, MA 02138; novalia.pishesha@childrens.harvard.edu hidde.ploegh@childrens.harvard.edu.
  • Harmand TJ; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
  • Rothlauf PW; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142.
  • Praest P; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115.
  • Alexander RK; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
  • van den Doel R; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110.
  • Liebeskind MJ; Program in Virology, Harvard Medical School, Boston, MA 02115.
  • Vakaki MA; Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • McCaul N; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
  • Wijne C; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
  • Verhaar E; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110.
  • Pinney W; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110.
  • Heston H; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
  • Bloyet LM; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
  • Pontelli MC; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
  • Ilagan MXG; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
  • Jan Lebbink R; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
  • Buchser WJ; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110.
  • Wiertz EJHJ; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110.
  • Whelan SPJ; High Throughput Screening Center, Washington University School of Medicine, St. Louis, MO 63110.
  • Ploegh HL; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110.
Proc Natl Acad Sci U S A ; 118(44)2021 11 02.
Article in English | MEDLINE | ID: covidwho-1470027
ABSTRACT
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (SpikeRBD) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHHMHCII). This vaccine elicits robust humoral and cellular immunity against SARS-CoV-2 and its variants. Both young and aged mice immunized with two doses of VHHMHCII-SpikeRBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHHMHCII-SpikeRBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pandemics / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Type of study: Observational study Topics: Vaccines / Variants Limits: Animals / Female / Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pandemics / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Type of study: Observational study Topics: Vaccines / Variants Limits: Animals / Female / Humans Language: English Year: 2021 Document Type: Article