Multivalent vaccines for rabies virus and coronaviruses
Inventors
Johnson, Reed F. • Schnell, Matthias • Hensley, Lisa E. • Wirblich, Christoph • COLEMAN, Christopher M. • Frieman, Matthew B.
Assignees
Thomas Jefferson University • University of Maryland Baltimore • US Department of Health and Human Services
Publication Number
US-11041170-B2
Publication Date
2021-06-22
Expiration Date
2037-03-31
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Abstract
The present disclosure provides methods and compositions for inducing an immune response that confers dual protection against infections by either or both of a rabies virus and a coronavirus, and/or which can be used therapeutically for an existing infection with rabies virus and/or a coronavirus to treat at least one symptom thereof and/or to neutralize or clear the infecting agents. In particular, the present disclosure provides a recombinant rabies virus vector comprising a nucleotide sequence encoding at least one coronavirus immunogenic glycoprotein fragment, as well as pharmaceutical compositions comprising the vaccine vectors.
Core Innovation
The invention provides novel recombinant vaccine constructs based on genetically modifying an attenuated rabies virus vaccine vector to express one or more coronavirus immunogenic glycoproteins or fragments thereof, such as the spike (S) glycoprotein from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) or Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV). These vaccine constructs are capable of inducing humoral and/or cellular immune responses against infections by rabies virus and/or coronaviruses. The vaccine can be used both prophylactically, to protect against future infections, and therapeutically, to aid in neutralizing or clearing existing infections.
The disclosure addresses the problem that current vaccine candidates for coronaviruses, such as MERS-CoV, have various limitations including concerns about safety, immunogenicity, pre-existing immunity to viral vectors, and the need for multiple inoculations. Moreover, existing vaccines often target only one pathogen. There is a need for additional vaccine candidates that can provide dual protection against rabies virus and coronaviruses, balancing ease of production, immunogenicity, and safety. Rabies virus-based vectors, both live attenuated and inactivated, have a proven safety record and have been used successfully as vaccines against other viruses such as Ebola virus.
Claims Coverage
The patent includes 21 claims focusing on a recombinant rabies virus vector expressing coronavirus immunogenic proteins and related compositions and methods. The main inventive features center on the vaccine vector construction, multivalent compositions, and therapeutic methods.
Recombinant rabies virus vector expressing specific coronavirus immunogenic proteins
A recombinant rabies virus vector comprising a nucleotide sequence encoding at least one immunogenic protein, wherein the protein has an amino acid sequence selected from SEQ ID NO: 8, 12, and 14.
Attenuated rabies virus genome used in the vaccine vector
The rabies virus genome incorporated in the vector is attenuated, including derivations from the SAD B19 live attenuated rabies virus vaccine strain.
Multivalent vaccine composition inducing immune response to rabies and coronavirus
A vaccine composition comprising a recombinant rabies virus vector expressing at least one coronavirus immunogenic protein selected from SEQ ID NO: 8, 12, and 14, capable of inducing an immune response protective against both rabies and coronavirus infections.
Recombinant rabies virus vector expressing additional coronavirus proteins or immunogenic fragments
The rabies virus genome further expresses one or more additional coronavirus proteins or immunogenic fragments thereof, including replicase polyproteins, E, N, M proteins, or nonstructural proteins from MERS-CoV or SARS-CoV.
Hosts and virions comprising the recombinant vaccine vector
Host cells comprising the recombinant rabies virus vector and isolated virions prepared from cells infected with the recombinant vector are claimed.
Methods of inducing immune responses and treating infections
Methods for inducing an immune response protective against coronavirus and/or rabies virus by administering the recombinant rabies virus vector vaccine compositions. This includes inducing neutralizing antibodies and treating infected subjects.
Live, replication-competent or replication-deficient rabies virus based vectors
The claims include live, replication-competent and replication-deficient rabies virus-based vectors expressing coronavirus glycoprotein or fragments thereof, specifically vectors having the nucleotide sequences of SEQ ID NO: 21, 23, or 24.
The claims define a recombinant rabies virus vector vaccine platform expressing coronavirus immunogenic proteins with attenuation and multivalent capability, compositions including such vectors and virions, and methods of immunization and treatment, emphasizing specific coronavirus glycoprotein sequences and SAD B19 derivation.
Stated Advantages
The vaccine platform can induce dual protection against both rabies virus and coronaviruses with a single immunization agent.
Attenuated rabies virus-based vectors possess a balance between immunogenicity and safety, reducing neurological damage risks.
The rabies virus-based vaccines are amenable to various formats, including live attenuated, replication-defective, and chemically inactivated vaccines.
The platform allows incorporation of coronavirus glycoprotein fragments that improve expression and incorporation into virions, enhancing vaccine efficacy.
The vaccine constructs have demonstrated strong immunogenicity and protective efficacy in mouse models.
Documented Applications
Preventive vaccination to induce humoral and/or cellular immune responses that protect subjects against subsequent infections by rabies virus and/or coronaviruses such as MERS-CoV and SARS-CoV.
Therapeutic vaccination to induce immune responses to aid neutralization or clearance of existing infections by rabies virus and/or coronaviruses, and to treat symptoms of such infections.
Use as a multivalent vaccine for animals and humans, addressing infections with both rabies virus and coronaviruses with a single vaccine composition.
Production of recombinant rabies virions expressing coronavirus antigens for use in chemically inactivated vaccine formulations.
Methods of detecting antibodies against rabies virus and coronaviruses to evaluate immune responses or exposure to the pathogens.
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