Generation of therapeutic antisera for emerging viral infections

Abstract

The recent Ebola virus outbreak has highlighted the therapeutic potential of antisera and renewed interest in this treatment approach. While human convalescent sera may not be readily available in the early stages of an outbreak, antisera of animal origin can be produced in a short time frame. Here, we compared adjuvanted virus-like particles (VLP) with recombinant modified vaccinia virus Ankara and vesicular stomatitis virus (VSV), both expressing the Ebola virus antigens. The neutralizing antibody titers of rabbits immunized with adjuvanted VLPs were similar to those immunized with the replication-competent VSV, indicating that presentation of the antigen in its native conformation rather than de novo antigen expression is essential for production of functional antibodies. This approach also yielded high-titer antisera against Nipah virus glycoproteins, illustrating that it is transferable to other virus families. Multiple-step immunoglobulin G purification using a two-step 20–40% ammonium sulfate precipitation followed by protein A affinity chromatography resulted in 90% recovery of functionality and sustained in vivo stability. Adjuvanted VLP-based immunization strategies are thus a promising approach for the rapid generation of therapeutic antisera against emerging infections.

Adjuvant formulated virus-like particles expressing native-like forms of the Lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity

“…Passive antibody therapy has long been used in the treatment and postexposure prophylaxis of various diseases, including viral infections and the development of heterologous polyclonal antibody preparations obtained from hyperimmunized animals against several highly pathogenic viruses such as Ebola, Junín, and Nipah 40,46,61,62 . Our VLP-based approach combines several advantages for therapeutic antibody production.…”

“…The purified GP VLPs were subsequently used to determine their suitability as immunogens. Therefore, two New Zealand White rabbits were immunized intramuscularly with 300 μg VLPs mixed in a 1:1 ratio with squalene-containing water-in-oil Sigma Adjuvant, which was recently demonstrated to enhance the induction of functional antibody titers against Ebola virus and Nipah virus 46 . Both rabbits received three booster injections with the adjuvanted GP VLP preparation at day 28, day 49, and day 70, as depicted in the schematic representation of the immunization scheme ( Fig.…”

“…For example, vaccination with VLPs derived from the highly pathogenic filoviruses, Ebola and Marburg virus, has shown protection from lethal virus infection in various animal models 43 – 45 . In addition to their suitability as vaccine platforms, VLPs have been used to generate pathogen-specific neutralizing antisera with therapeutic potential for the treatment of viral infections 46 . We previously described that the sole expression of LASV GP in mammalian cells is sufficient to produce VLPs displaying GP in its trimeric form on the envelope surface that closely mimic the structure of the virion-associated spike 47 – 49 .…”

Recent biotechnological approaches for treatment of novel COVID-19: from bench to clinical trial

“…Immunization of colossal animals, for instance, sheep and goats with the COVID-19 S protein and a short time later collecting the produced polyclonal antibodies from animals could be an elective system for the production is killing antibodies versus the COVID-19 S protein (Schmidt et al 2018). This procedure in light of the various favorable circumstances, for instance, unraveling creation and amassing may serve as an accelerated organization in the setting of an eruption, regardless, it has compelled guarantees that each animal would convey slaughtering antisera, or what the neutralizing operator titer would be in each animal (Jahrling et al 1996).…”

Strategies and Challenges to Develop Therapeutic Candidates against COVID-19 Pandemic

“…For quick production of antibodies, lead therapeutic candidates can be utilized for protein expression in bacteria, yeast or insect cells [49]. A much promising approach for producing neutralizing antibodies can be immunizing sheep, goat, cow or large animals with the SARS-CoV-2 proteins followed by purification of antibodies from the animals [50]. The challenge associated with the use of large animals is that there is no guarantee that they will produce neutralizing antisera or not.…”