Antibody therapeutics · 2026
A hyperimmune ovine antibody-based therapeutic candidate against Crimean-Congo haemorrhagic fever virus targeted to the Gn and Gc glycoproteins: high antibody levels with neutralization activity but lack of protective efficacy in a mouse model.
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Kennedy Emma, Findlay-Wilson Stephen, Webster Sarah, Rajabzadeh Annahita, Fotheringham Susan, Easterbrook Linda, Chambers Adam, Aksular Mine, Possee Robert, Smith Sandra, Pope Neville, Griffiths Aled, Arnold Ulrike, Jackson David, Ruedas-Torres Inés, Salguero Francisco Javier, Dowall Stuart
Аннотация
BACKGROUND: Crimean-Congo haemorrhagic fever virus (CCHFV) is a tick-borne pathogen that has a wide geographical range and has the potential to cause severe disease in those infected. There are no currently approved vaccines or therapeutics, so the development and assessment of new approaches are urgently required.
METHODS: A polyclonal antibody-based therapeutic was developed based on immunization of sheep with the major glycoprotein antigens from CCHFV. Along with purified immunoglobulin G (IgG) from hyperimmune sera, fragmentation of the F(ab')2 region was also performed. The pharmacokinetic properties were assessed in mice, and efficacy was ascertained in a live CCHFV challenge model.
RESULTS: Candidate polyclonal antibody-based therapies were developed, demonstrating strong binding to the CCHFV envelope glycoprotein and neutralizing activity. The ovine whole IgG demonstrated stability post-delivery compared to a rapid reduction of the F(ab')2 fragment in the circulation. Efficacy testing when delivered either as a single dose before challenge or as daily dosing for 7 days starting on the day of challenge showed no demonstrable evidence of protection against infection.
CONCLUSIONS: Despite protection observed from vaccine candidates using the CCHFV glycoprotein as an antigen and administration of convalescent sera, the ovine antibody-based therapeutics did not confer similar efficacious effects in the mouse preclinical model.
METHODS: A polyclonal antibody-based therapeutic was developed based on immunization of sheep with the major glycoprotein antigens from CCHFV. Along with purified immunoglobulin G (IgG) from hyperimmune sera, fragmentation of the F(ab')2 region was also performed. The pharmacokinetic properties were assessed in mice, and efficacy was ascertained in a live CCHFV challenge model.
RESULTS: Candidate polyclonal antibody-based therapies were developed, demonstrating strong binding to the CCHFV envelope glycoprotein and neutralizing activity. The ovine whole IgG demonstrated stability post-delivery compared to a rapid reduction of the F(ab')2 fragment in the circulation. Efficacy testing when delivered either as a single dose before challenge or as daily dosing for 7 days starting on the day of challenge showed no demonstrable evidence of protection against infection.
CONCLUSIONS: Despite protection observed from vaccine candidates using the CCHFV glycoprotein as an antigen and administration of convalescent sera, the ovine antibody-based therapeutics did not confer similar efficacious effects in the mouse preclinical model.