A recent animal study by researchers from the University of Hong Kong (HKU) shows persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in nasal turbinates of hamsters for the first 1–3 days following administration of human neutralizing antibody (HuNAb) therapy and spike protein–based DNA vaccine.
“The presence of high antibody titre generated after antibody therapy or vaccination does not translate to full protection against SARS-CoV-2 infection in the upper respiratory tract [URT]. Apart from vaccination, mask wearing and hand hygiene should still be in place to prevent the spread of the virus,” said Professor Kwok-Yung Yuen of the Department of Microbiology, HKU.
“Although several coronavirus disease 2019 [COVID-19] vaccines have been approved for emergency use, vaccine-induced protection against asymptomatic SARS-CoV-2 infection has remained largely unsuccessful,” said Professor Zhiwei Chen of the Department of Microbiology, HKU. “Persistence of high SARS-CoV-2 viral load in nasal turbinates of hamsters demonstrated in our study explains the challenge in providing full protection against COVID-19, and highlights the importance of COVID-19 mucosal vaccine development.”
In the study, three potent receptor binding protein (RBD)–specific HuNAb (IC50 range, 0.0007–0.35 µg/mL), namely, ZDY20, ZB8 and 2-15, and four full‐length spike protein–based DNA vaccines were injected intraperitoneally and intramuscularly to male and female Syrian hamsters (age, 6–10 weeks) in both prophylactic and therapeutic settings. [Cell Host Microbe 2021, doi: 10.1016/j.chom.2021.02.019]
ZDY20 was obtained by cloning antibodies from peripheral blood mononuclear cells from 12 convalescent COVID-19 patients (mean age, 59 years; mean duration of COVID-19 after symptom onset, 19 days) in Hong Kong.
In hamsters given prophylactic ZDY20 injection, reverse transcription polymerase chain reaction analysis showed an average 3-log reduction of SARS-CoV-2 viral load at 4 days post-infection (dpi) in lungs following intranasal injection of 105 plaque-forming units (PFU) of live SARS-CoV-2. However, no significant reduction in viral load was found in nasal turbinates and trachea, suggesting limited efficacy of prophylactic ZDY20 against SARS-CoV-2 entry in the URT.
Pathological assessment also showed limited efficacy of high-dose (10 mg/kg) prophylactic ZDY20 injection against SARS-CoV-2 in nasal turbinates of hamsters, with extensive submucosal immune cell infiltration and diffuse viral anti-nucleocapsid (NP) expression seen in respiratory and olfactory epithelium of nasal turbinates.
Prophylactic injection of ZB8 and 2-15 to hamsters intranasally challenged with SARS-CoV-2 showed similar effectiveness in reducing viral load and NP cells in lungs, but not in nasal turbinates at 4 dpi.
DNA vaccination, which induced RBD binding and neutralizing antibodies, was also shown to be ineffective in providing mucosal protection of nasal turbinates in hamsters at 4 dpi following intranasal challenge with SARS-CoV-2.
Early commencement (ie, within 1 dpi vs 3 dpi) of ZDY20 10 mg/kg as SARS-CoV-2 treatment in infected hamsters showed greater reduction in mean viral load across lung, trachea and nasal turbinates, with significant reduction in mean viral load in nasal turbinates and trachea (0.7 logs; p<0.05) and lung (1.2 logs; p<0.01) compared with the control group at 1 dpi. Nonetheless, SARS-CoV-2 infection in nasal turbinates of hamsters persisted through 1–3 dpi, suggesting ineffectiveness of systemic HbNAb in outcompeting viral replication within the nasal mucosa.
Presence of HuNAb homogenates in nasal turbinate (p<0.0001) and lungs (p=0.0005) of hamsters may account for significant reduction in infectious viral particles.