Fc-Based Recombinant Henipavirus Vaccines Elicit Broad Neutralizing Antibody Responses in Mice

Abstract

The genus Henipavirus (HNVs) includes two fatal viruses, namely Nipah virus (NiV) and Hendra virus (HeV). Since 1994, NiV and HeV have been endemic to the Asia-Pacific region and responsible for more than 600 cases of infections. Two emerging HNVs, Ghana virus (GhV) and Mojiang virus (MojV), are speculated to be associated with unrecognized human diseases in Africa and China, respectively. Despite many efforts to develop vaccines against henipaviral diseases, there is presently no licensed human vaccine. As HNVs are highly pathogenic and diverse, it is necessary to develop universal vaccines to prevent future outbreaks. The attachment enveloped glycoprotein (G protein) of HNVs mediates HNV attachment to the host cell's surface receptors. G proteins have been used as a protective antigen in many vaccine candidates for HNVs. We performed quantitative studies on the antibody responses elicited by the G proteins of NiV, HeV, GhV, and MojV. We found that the G proteins of NiV and HeV elicited only a limited cross-reactive antibody response. Further, there was no cross-protection between MojV, GhV, and highly pathogenic HNVs. We then constructed a bivalent vaccine where the G proteins of NiV and HeV were fused with the human IgG1 Fc domain. The immunogenicity of the bivalent vaccine was compared with that of monovalent vaccines. Our results revealed that the Fc-based bivalent vaccine elicited a potent antibody response against both NiV and HeV. We also constructed a tetravalent Fc heterodimer fusion protein that contains the G protein domains of four HNVs. Immunization with the tetravalent vaccine elicited broad antibody responses against NiV, HeV, GhV, and MojV in mice, indicating compatibility among the four antigens in the Fc-fusion protein. These data suggest that our novel bivalent and tetravalent Fc-fusion proteins may be efficient candidates to prevent HNV infection.

Recombinant Fc-fusion vaccine of RBD induced protection against SARS-CoV-2 in non-human primate and mice

“…Although there is no FDA approved Fc-fusion vaccine in clinic, the explosion of vaccine development fused with Fc is active and ongoing. A number of studies have been initiated on the development of vaccines against Ebola 34 , HIV 35 , influenza 36 , SARS-CoV 13 , tuberculosis 37 as well as RSV 38 , HNV 39 . Currently, although other options, such as IgG3, IgA, and IgM are being explored, all commercial therapeutics use the Fc domain from human IgG1 40 .…”

Peptibody Based on FGFR1-Binding Peptides From the FGF4 Sequence as a Cancer-Targeting Agent

“…The proposed application of these receptor-binding peptibodies is as cytotoxic drug carriers and conjugated with monomethylauristatin E (MMAE). Although auristatin cannot be used as a free drug due to its toxicity and adverse side effects, it is successfully used in combination with antibodies ( Li et al, 2020 ; Zhao et al, 2020 ; and Currier et al, 2016 ). Two antibody–MMAE conjugates are approved for clinical use, and many more are tested in preclinical and clinical trials ( Shefet-Carasso and Benhar, 2015 ; Deeks, 2019 ).…”

Medical countermeasures against henipaviruses: a review and public health perspective

“… ‡ Reference data for monoclonal antibodies are based on data available in the public domain for bamlanimivab (Eli Lilly, Indianapolis, IN, USA) and casirivimab plus imdevimab (REGN-COV2 antibody cocktail [Regeneron, Tarrytown, NY, USA]). 90 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 § Costs exclude expenses related to vaccine delivery, transport, refrigeration, and administration. …”