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A Bacteriophage-Based, Highly Efficacious, Needle- and Adjuvant-Free, Mucosal COVID-19 Vaccine.
Zhu, Jingen; Jain, Swati; Sha, Jian; Batra, Himanshu; Ananthaswamy, Neeti; Kilgore, Paul B; Hendrix, Emily K; Hosakote, Yashoda M; Wu, Xiaorong; Olano, Juan P; Kayode, Adeyemi; Galindo, Cristi L; Banga, Simran; Drelich, Aleksandra; Tat, Vivian; Tseng, Chien-Te K; Chopra, Ashok K; Rao, Venigalla B.
  • Zhu J; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of Americagrid.39936.36, Washington, DC, USA.
  • Jain S; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of Americagrid.39936.36, Washington, DC, USA.
  • Sha J; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Batra H; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of Americagrid.39936.36, Washington, DC, USA.
  • Ananthaswamy N; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of Americagrid.39936.36, Washington, DC, USA.
  • Kilgore PB; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Hendrix EK; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Hosakote YM; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Wu X; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of Americagrid.39936.36, Washington, DC, USA.
  • Olano JP; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Kayode A; Department of Biology, Western Kentucky University, Bowling Green, Kentucky, USA.
  • Galindo CL; Department of Biology, Western Kentucky University, Bowling Green, Kentucky, USA.
  • Banga S; Department of Biology, Western Kentucky University, Bowling Green, Kentucky, USA.
  • Drelich A; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Tat V; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Tseng CK; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Chopra AK; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA.
  • Rao VB; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, Texas, USA.
mBio ; 13(4): e0182222, 2022 08 30.
Article in English | MEDLINE | ID: covidwho-1962098
ABSTRACT
The U.S. Food and Drug Administration-authorized mRNA- and adenovirus-based SARS-CoV-2 vaccines are intramuscularly injected in two doses and effective in preventing COVID-19, but they do not induce efficient mucosal immunity or prevent viral transmission. Here, we report the first noninfectious, bacteriophage T4-based, multicomponent, needle- and adjuvant-free, mucosal vaccine harboring engineered Spike trimers on capsid exterior and nucleocapsid protein in the interior. Intranasal administration of two doses of this T4 SARS-CoV-2 vaccine 21 days apart induced robust mucosal immunity, in addition to strong systemic humoral and cellular immune responses. The intranasal vaccine induced broad virus neutralization antibody titers against multiple variants, Th1-biased cytokine responses, strong CD4+ and CD8+ T cell immunity, and high secretory IgA titers in sera and bronchoalveolar lavage specimens from vaccinated mice. All of these responses were much stronger in intranasally vaccinated mice than those induced by the injected vaccine. Furthermore, the nasal vaccine provided complete protection and sterilizing immunity against the mouse-adapted SARS-CoV-2 MA10 strain, the ancestral WA-1/2020 strain, and the most lethal Delta variant in both BALB/c and human angiotensin converting enzyme (hACE2) knock-in transgenic mouse models. In addition, the vaccine elicited virus-neutralizing antibodies against SARS-CoV-2 variants in bronchoalveolar lavage specimens, did not affect the gut microbiota, exhibited minimal lung lesions in vaccinated and challenged mice, and is completely stable at ambient temperature. This modular, needle-free, phage T4 mucosal vaccine delivery platform is therefore an excellent candidate for designing efficacious mucosal vaccines against other respiratory infections and for emergency preparedness against emerging epidemic and pandemic pathogens. IMPORTANCE According to the World Health Organization, COVID-19 may have caused ~15-million deaths across the globe and is still ravaging the world. Another wave of ~100 million infections is predicted in the United States due to the emergence of highly transmissible immune-escaped Omicron variants. The authorized vaccines would not prevent these transmissions since they do not trigger mucosal immunity. We circumvented this limitation by developing a needle-free, bacteriophage T4-based, mucosal vaccine. This intranasally administered vaccine generates superior mucosal immunity in mice, in addition to inducing robust humoral and cell-mediated immune responses, and provides complete protection and sterilizing immunity against SARS-CoV-2 variants. The vaccine is stable, adjuvant-free, and cost-effectively manufactured and distributed, making it a strategically important next-generation COVID vaccine for ending this pandemic.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Bacteriophages / COVID-19 Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: MBio Year: 2022 Document Type: Article Affiliation country: Mbio.01822-22

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Bacteriophages / COVID-19 Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: MBio Year: 2022 Document Type: Article Affiliation country: Mbio.01822-22