Summary
The mRNA and adenovirus-based SARS-CoV-2 vaccines, authorized by the US Food and Drug Administration, are injected intramuscularly in two doses and are effective in preventing COVID-19, but do not induce efficient mucosal immunity nor prevent viral transmission. Here, we report the first non-infectious , bacteriophage T4-based, multicomponent, needle-free and adjuvant-free mucosal vaccine harboring engineered Spike trimers on the outside of the capsid and the nucleocapsid protein on the inside.
Intranasal administration of two doses of this T4 SARS-CoV-2 vaccine 21 days apart induced strong mucosal immunity in addition to strong systemic humoral and cellular immune responses.
The intranasal vaccine induced broad titers of virus neutralizing antibodies against multiple variants, Th1-biased cytokine responses, strong CD4+ and CD8+ T cell immunity, and high secretory IgA titers in sera and bronchoalveolar lavage samples from vaccinated mice.
All of these responses were much stronger in mice vaccinated intranasally 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 more lethal Delta variant in both BALB/c and angiotensin-converting enzyme. human (hACE2) knock-in transgenic mouse models .
Furthermore, the vaccine elicited virus-neutralizing antibodies against SARS-CoV-2 variants in bronchoalveolar lavage samples, did not affect gut microbiota, showed minimal lung lesions in vaccinated and challenged mice, and is completely stable at room temperature. Therefore, this modular needle-free T4 phage mucosal vaccine delivery platform is an excellent candidate for designing effective 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 worldwide and continues to wreak havoc around the world. Another wave of ~100 million infections is predicted in the United States due to the emergence of highly transmissible immune escape 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 humoral and solid 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 to end this pandemic. |
Comments
New research shows that a needle-free mucosal bacteriophage (phage)-based COVID-19 vaccine is effective against SARS-CoV-2 infection. The findings were published in mBio , an open access journal of the American Society for Microbiology.
In recent years, the Food and Drug Administration has authorized mRNA and adenovirus-based SARS-CoV-2 vaccines. These vaccines are injected intramuscularly in 2 or more doses and are effective in preventing COVID-19, but do not induce effective mucosal immunity or prevent viral transmission.
In the new study, lead study authors Venigalla B. Rao, Ph.D., of the Bacteriophage Medical Research Center, Department of Biology, Catholic University of America, Washington, DC, and Ashok K. Chopra, Ph. D., CSc, Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, and colleagues report the first non-infectious, bacteriophage T4-based, multicomponent, needle-free, and adjuvant-free mucosal vaccine. Both senior authors are elected members of the American Academy of Microbiology.
In experiments performed in mice , intranasal administration of 2 doses of the T4-COVID-19 phage vaccine 21 days apart induced strong mucosal immunity, in addition to strong systemic humoral and cellular immune responses.
The intranasal vaccine induced broad titers of virus-neutralizing antibodies against multiple variants and triggered Th1 cytokine responses, strong CD4+ and CD8+ T cell immunity, and high secretory IgA titers in sera and bronchoalveolar lavage of vaccinated mice. All of these responses were much stronger in mice vaccinated intranasally 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 more lethal Delta variant in mouse models.
Furthermore, the T4-COVID-19 vaccine elicited broad virus-neutralizing antibodies against SARS-CoV-2 variants in sera and bronchoalveolar lavage, did not affect the gut microbiota, showed minimal lung lesions in vaccinated and challenged mice, and is stable at temperature. atmosphere.
“This intranasally administered vaccine generates superior mucosal immunity in mice, in addition to inducing humoral and solid 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-19 vaccine to end this pandemic,” said Drs. Rao and Chopra. “This modular, needle-free T4 phage mucosal vaccine delivery platform is an excellent candidate for designing effective mucosal vaccines against other respiratory infections and for emergency preparedness against emerging epidemic and pandemic pathogens.”
