Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants

Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing antibodies.This highlights a critical need to discover new therapeutic agents to overcome the variants mutations.Despite the availability of vaccines against coronavirus disease 2019(COVID-19),the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-Co V-2 variants infection.Here,we show that the nasal delivery of two previously characterized broadly neutralizing antibodies(F61 and H121)protected K18-h ACE2 mice against lethal challenge with SARS-Co V-2 variants.The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain(WIV04)and multiple variants,including beta(B.1.351),delta(B.1.617.2),and omicron(B.1.1.529)at 200or 1000 TCID_(50),and the minimum antibody administration doses(5-1.25 mg/kg body weight)were also evaluated with delta and omicron challenge.Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight,and corresponding mice lung viral RNA showed negative,with almost all alveolar septa and cavities remaining normal.Furthermore,low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants,whereas the F61/H121 combination showed excellent results against omicron infection.Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-Co V-2 variants infection.

Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants

Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries.Of them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co V-2.Following structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding domain.Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co V-2.Importantly,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain B.1.617.The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral escape.Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants.

Hemorrhagic Fever with Renal Syndrome — Liaoning Province, China, 1999−2018

Summary What is already known on this topic?Hemorrhagic fever with renal syndrome(HFRS)is endemic in Liaoning Province.Both Seoul and Hantaan virus are circulating in rodents,and epidemic outbreaks and sporadic cases have been recorded every year since the disease was recognized.