Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC 50 range, 0.0007-0.35 μg/ml) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain (RBD). Prophylactic intraperitoneal or intranasal injection of individual HuNAb or DNA vaccination significantly reduces infection in the lungs but not in the nasal turbinates of hamsters intranasally challenged with SARS-CoV-2. Although postchallenge HuNAb therapy suppresses viral loads and lung damage, robust infection is observed in nasal turbinates treated within 1-3 days. Our findings demonstrate that systemic HuNAb suppresses SARS-CoV-2 replication and injury in lungs; however, robust viral infection in nasal turbinate may outcompete the antibody with significant implications to subprotection, reinfection and vaccine.

Antibody Responses to SARS-CoV-2 mRNA Vaccines Are Detectable in Saliva

“…Additional studies in this area are justified, particularly now that key target cells for SARS-CoV-2 infection in the oral cavity have been identified [5]. A report on SARS-CoV-2 infection in rhesus macaques shows that virus can still replicate in nasal turbinates even when it is suppressed in the lungs by passively transferred NAbs [28]. Assays of vaccine-induced antibodies extracted from NP swabs might provide useful information, although Ig concentrations in tissue sites, eg, intra-mucosal interstitial fluids, may be impossible to measure by swab-sampling and extraction.…”

COVID-19 Vaccines: A Review of the Safety and Efficacy of Current Clinical Trials

“…Likewise, influenzae carries similar pathogenesis as SARS-CoV-2. However, the experience of influenzae vaccinations (inactivated virus) shows that vaccinations reduced major cardiovascular events significantly, and has become part of the routine care of patients with chronic cardiovascular conditions [ 59 ]. COVID-19 vaccinations do not follow the typical trend of influenzae.…”

Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes

“…As a direct adaptation against antibody pressure, however, RBS is also the primary region where a number of convergent mutations have arisen in circulating variants of SARS-CoV-2. These variants may enhance ACE2 binding leading to higher transmissibility, elude many neutralizing mAbs, including those under clinical development, and substantially reduce the neutralizing activities of convalescent and vaccine-elicited polyclonal sera [19][20][21] . These adaptations led to the global emergence of convergent circulating variants of concern, including the UK strain (B.1.1.7), the South Africa strain (B.1.351), and the Brazil strain (P.1) [22][23][24] .…”