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.
Highlights
IgG levels are commonly monitored in serum to assess immunity, this isotype, unlike IgA, is not secreted into the mucosal lumen via the polymeric Ig receptor, and must rely on passive transport to accumulate at these sites
Dimeric IgA in secretions have a fundamental role in SARS-CoV-2 neutralization [44]—after infection, very high serum IgA levels develop in patients with severe
BNT162b2 induces anti-Spike IgG1, IgG3, and IgA1 in serum, but only IgG in saliva
Summary
Intramuscularly injected COVID-19 vaccines (summarized in Figure 1) effectively reduce severity of disease and symptomatic cases, but still allow for asymptomatic infection. Intramuscular vaccination does provide some measure of protection in the nasal airways against SARS-CoV-2, as evident by reduction in symptomatic disease after infection. PCR to improve estimates of vaccine efficacy against SARS-CoV-2 infection Such viral-load measures could be used to estimate (VE)against againsttransmission, SARS-CoV-2 assuming infection. SARS-CoV-2 lungdelivery injury, of butanti-SARS-CoV-2 allowing robust mAbs infection in nasal in animal models [10] For replication this reason,and topical is being turbinates[11]. In the case of SARS-CoV-2 there is evidence that initial infection and replication occurs in the nasal ciliated cells [14], a site that is not accessible to serum IgG unless there is inflammatory damage to the mucosal tissues that allows transudation of serum proteins to the site. Current vaccines for COVID-19 prevent disease but not infection
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