Zika vaccines and immunogenic compositions, and methods of using the same
Inventors
Livengood, Jill A. • GIEBLER, Holli • BALDWIN, Whitney • Dean, Hansi • Kinney, Claire Y. H.
Assignees
Takeda Vaccines Inc • US Department of Health and Human Services
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11648304-B2
Publication Date
2023-05-16
Expiration Date
2038-11-05
Abstract
The present disclosure relates to Zika virus vaccines and immunogenic compositions having one or more antigens from a Zika virus (e.g., a Zika virus clonal isolate, a non-human cell adapted Zika virus, etc.), and methods of manufacture, formulation, testing, and uses thereof.
Core Innovation
The invention relates to Zika virus vaccines and immunogenic compositions comprising one or more antigens from a Zika virus, including genetically stable non-human cell adapted Zika viruses harboring an adaptation mutation in the Non-structural protein 1 (NS1), and Zika virus clonal isolates that are genetically homogeneous and purified away from adventitious agents. These vaccines may be whole inactivated Zika viruses and are useful for treating and preventing Zika virus infection and inducing immune responses in subjects, including humans.
The problem being solved arises from the instability of recombinant Zika virus strains, such as strain PRVABC59, which previously required a two plasmid system for vaccine development, which is less desirable. There is a need for genetically stable Zika virus vaccines that do not require a two-vector system. The invention addresses this by providing a stable non-human cell adapted Zika virus with a mutation in NS1 and wild-type envelope protein, enabling the use of a single virus system for vaccine production.
The disclosure shows that clonal isolation of Zika virus strains allows for purification away from adventitious agents and generation of genetically homogeneous populations. Clonal isolates harboring an adaptation mutation in NS1 grow well in Vero cells to high titers and are genetically stable without detectable mutations in the envelope protein. The NS1 mutation enhances genetic stability, viral replication, and reduces undesirable mutations, such as in the envelope protein. Vaccines containing antigens from these stable, adapted Zika viruses induce robust immune responses and protection from infection.
Claims Coverage
The patent contains one independent claim covering an immunogenic composition and a method to induce an immune response using Zika virus with a specific NS1 mutation. Two main inventive features are identified.
Immunogenic composition comprising a genetically adapted inactivated Zika virus
The immunogenic composition contains a Zika virus with a tryptophan to glycine mutation at position 98 (Trp98Gly) of NS1 (SEQ ID NO: 1 or corresponding position), where the virus is an inactivated whole virus, chemically inactivated with formaldehyde, optionally having an envelope protein with high sequence identity to SEQ ID NO: 2 or an identical envelope sequence as SEQ ID NO: 2, and optionally comprising an adjuvant such as aluminum hydroxide.
Method of inducing an immune response using the immunogenic composition
The method involves administering an immunogenic amount of the immunogenic composition as claimed, which induces the generation of neutralizing antibodies to Zika virus in a subject. Administration can be via a prime and boost schedule.
The claims cover compositions comprising an inactivated, genetically stable Zika virus with a NS1 Trp98Gly mutation and methods of use to induce an immune response in subjects, emphasizing the specifics of the mutation, virus inactivation, adjuvant inclusion, and immunogenic efficacy.
Stated Advantages
The NS1 adaptation mutation enhances genetic stability of the Zika virus compared to viruses lacking the mutation.
The mutation enhances viral replication compared to Zika virus lacking the mutation.
The stable virus reduces or inhibits occurrence of undesirable mutations, such as mutations within the envelope protein.
Clonal isolation allows purification away from contaminating adventitious agents and production of genetically homogeneous viral populations.
Vaccines comprising antigens from the adapted Zika virus induce robust immune responses and provide significant protection from Zika virus infection at both low and high doses.
Documented Applications
Vaccines and immunogenic compositions for treating or preventing Zika virus infection in subjects, including humans.
Inducing protective immune responses against Zika virus in subjects in need thereof.
Use in immunizing pregnant subjects or those intending to become pregnant.
Use of purified inactivated whole Zika virus vaccines derived from stable, adapted Zika virus strains for immunization.
Interested in licensing this patent?