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Review
. 2022 Jan 19;14(2):187.
doi: 10.3390/v14020187.

Mucosal Vaccines, Sterilizing Immunity, and the Future of SARS-CoV-2 Virulence

Daniele Focosi  1 , Fabrizio Maggi  2 , Arturo Casadevall  3
Affiliations
Review

Mucosal Vaccines, Sterilizing Immunity, and the Future of SARS-CoV-2 Virulence

Daniele Focosi et al. Viruses. .

Abstract

Sterilizing immunity after vaccination is desirable to prevent the spread of infection from vaccinees, which can be especially dangerous in hospital settings while managing frail patients. Sterilizing immunity requires neutralizing antibodies at the site of infection, which for respiratory viruses such as SARS-CoV-2 implies the occurrence of neutralizing IgA in mucosal secretions. Systemic vaccination by intramuscular delivery induces no or low-titer neutralizing IgA against vaccine antigens. Mucosal priming or boosting, is needed to provide sterilizing immunity. On the other side of the coin, sterilizing immunity, by zeroing interhuman transmission, could confine SARS-CoV-2 in animal reservoirs, preventing spontaneous attenuation of virulence in humans as presumably happened with the endemic coronaviruses. We review here the pros and cons of each vaccination strategy, the current mucosal SARS-CoV-2 vaccines under development, and their implications for public health.

Keywords: BNT162b2; COVID-19; IgA; IgG; SARS-CoV-2; intranasal vaccine; mRNA-1273; mucosal vaccines; neutralizing antibody; oral vaccines; sterilizing immunity.

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Conflict of interest statement

D.F. received fees for the advisory board by Novavax. The other authors declare no conflict of interest related to this manuscript.

Figures

Figure 1
Figure 1
Schematic representation of mechanisms of action of currently approved intramuscular vaccines and next-generation mucosal vaccines.
See this image and copyright information in PMC

References

    1. Ewer K.J., Barrett J.R., Belij-Rammerstorfer S., Sharpe H., Makinson R., Morter R., Flaxman A., Wright D., Bellamy D., Bittaye M., et al. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat. Med. 2021;27:270–278. doi: 10.1038/s41591-020-01194-5. - DOI - PubMed
    1. Hart T.K., Cook R.M., Zia-Amirhosseini P., Minthorn E., Sellers T.S., Maleeff B.E., Eustis S., Schwartz L.W., Tsui P., Appelbaum E.R., et al. Preclinical efficacy and safety of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys. J. Allergy Clin. Immunol. 2001;108:250–257. doi: 10.1067/mai.2001.116576. - DOI - PubMed
    1. Peebles R.S., Jr., Liu M.C., Lichtenstein L.M., Hamilton R.G. IgA, IgG and IgM quantification in bronchoalveolar lavage fluids from allergic rhinitics, allergic asthmatics, and normal subjects by monoclonal antibody-based immunoenzymetric assays. J. Immunol. Methods. 1995;179:77–86. doi: 10.1016/0022-1759(94)00275-2. - DOI - PubMed
    1. Wu H., Pfarr D.S., Johnson S., Brewah Y.A., Woods R.M., Patel N.K., White W.I., Young J.F., Kiener P.A. Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J. Mol. Biol. 2007;368:652–665. doi: 10.1016/j.jmb.2007.02.024. - DOI - PubMed
    1. Borrok M.J., DiGiandomenico A., Beyaz N., Marchetti G.M., Barnes A.S., Lekstrom K.J., Phipps S.S., McCarthy M.P., Wu H., Dall'Acqua W.F., et al. Enhancing IgG distribution to lung mucosal tissue improves protective effect of anti-pseudomonas aeruginosa antibodies. JCI Insight. 2018;3:e97844. doi: 10.1172/jci.insight.97844. - DOI - PMC - PubMed