Review
Version 1
Preserved in Portico This version is not peer-reviewed
COVID-19 Vaccines for Optimizing Immunity in the Upper Respiratory Tract
Version 1
: Received: 10 October 2023 / Approved: 11 October 2023 / Online: 11 October 2023 (10:52:38 CEST)
A peer-reviewed article of this Preprint also exists.
Ramasamy, R. COVID-19 Vaccines for Optimizing Immunity in the Upper Respiratory Tract. Viruses 2023, 15, 2203. Ramasamy, R. COVID-19 Vaccines for Optimizing Immunity in the Upper Respiratory Tract. Viruses 2023, 15, 2203.
Abstract
Rapid development and deployment of vaccines greatly reduced mortality and morbidity during the COVID-19 pandemic. The most widely used COVID-19 vaccines approved by national regulatory authorities require intramuscular administration. SARS-CoV-2 initially infects the upper respiratory tract where the infection can be eliminated with little or no symptoms by an effective immune response. Failure to eliminate SARS-CoV-2 in the upper respiratory tract results in lower respiratory tract infections that can lead to severe disease and death. Presently used intramuscularly administered COVID-19 vaccines are effective in reducing severe disease and mortality but are not entirely able to prevent asymptomatic and mild infections as well as person to person transmission of the virus. Individual and population differences also influence susceptibility to infection and the propensity to develop severe disease. This article provides a perspective on the nature and the mode of delivery COVID-19 vaccines that can optimize protective immunity in the upper respiratory tract to reduce infections and virus transmission as well as severe disease.
Keywords
adaptive immunity to COVID-19; clinical vaccine trials; COVID-19; COVID-19 vaccines; innate immunity to COVID-19; mucosal vaccines; nasal vaccines; SARS-CoV-2; upper respiratory tract immunity; vaccine safety
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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- mucosal immunity in the URT is primarily mechanistic/physical barrier – nasal hairs, mucus produced by goblet cells, ciliary beating of motile cilia, etc. and only a secondary – immunologic barrier, for maintenance of bodily integrity. This makes any inoculation strategies irrelevant because role of immunological barrier plays a non-essential role in maintaining of bodily integrity against external pathogens, when anti-septic nasal or oral sprays (hypertonic saline, hydrogen peroxide, povidone iodine, nitric oxide, etc.) are more potent agents than any vaccine no matter what vaccination strategy is used (prime and spike, prime and pull, for instance) or what adjuvants are added;
- olfactory mucosa is distinct immunological department from systemic immunity separated by blood-endothelial barrier, which restricts monomeric Abs reaching mucosa of the URT. Even those Abs from the circulation that reach the mucosa of the URT have short half-live and poor neutralising capacity in comparison to polymeric secretory IgA produced by tissue resident B cells there;
- best mucosal immunity is in those having an innate immunity in good shape. It is not adaptive immunity that constitutes effective immunity in the URT. Therefore, vaccines that induce high titter of poly-specific Abs, non-antigen specific effector cells and otherwise trains innate immunity are more potent for inducing effective immune response in the URT (e.g. BCG, BPZE1 vaccines). Why would anyone then spend efforts in vain for development and administering parenteral antigen-specific vaccine against airborne respiratory pathogen?