Polypeptide vaccine and vaccination strategy against mycobacterium
Inventors
Sable, Suraj • Plikaytis, Bonnie B. • Shinnick, Thomas M. • Amara, Rama Rao • Cheruvu, Manl
Assignees
Emory University • Centers of Disease Control and Prevention CDC • US Department of Health and Human Services
Publication Number
US-8741313-B2
Publication Date
2014-06-03
Expiration Date
2029-01-12
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Abstract
A vaccine is provided wherein a polypeptide or combination of peptides from M. tuberculosis is administered to a subject to elicit an immune response. The polypeptide vaccine is administered as part of a prime-boost strategy with BCG vaccine to increase the immunoprotection in a subject such that prevention or elimination of disease is achieved. Finally, a pharmaceutical package is provided that encompasses a polypeptide vaccine for M. tuberculosis that when administered to a subject elicits immunoprotection.
Core Innovation
The invention provides a vaccine that includes at least one M. tuberculosis polypeptide to increase the immune response in a subject. The polypeptides include, but are not limited to, Ag85A, Ag85B, MPT-64, Pst-S1, Apa, GroES, GroEL, Dnak, CFP-10, Rv0831c, and Rv1324, or portions, combinations, and multiples thereof. These polypeptides are optionally recombinant and may include purification tags. The vaccine may also contain an emulsification agent such as supramolecular biovectors, nanoparticles, or liposomes, and an adjuvant like dimethyl dioctadecyl-ammonium bromide (DDA), monophosphoryl lipid A (MPL), or other known adjuvants.
The problem addressed is the limited and variable efficacy of the current BCG vaccine against adult pulmonary tuberculosis, especially in developing countries and in the context of increasing HIV rates. Existing vaccines offer inconsistent protection, and the variable success of subunit vaccines, recombinant bacterial vector vaccines, DNA vaccines, and prime-boost strategies points to a need for an improved tuberculosis vaccine and vaccination strategy that elicits a robust immune response and protection.
The invention proposes a prime-boost vaccination strategy wherein a recombinant M. tuberculosis polypeptide vaccine is administered alone or in conjunction with the BCG vaccine by various routes including intranasal, subcutaneous, and others. Notably, the invention discloses use of non-glycosylated polypeptides produced in systems like E. coli that surprisingly elicit robust immunogenicity. The vaccine can be multi-component with a synergistic immunogenic effect, and administration timing and delivery route can vary to optimize immune response.
Claims Coverage
The patent contains multiple independent claims covering vaccines comprising polypeptides from M. tuberculosis, pharmaceutical packages, and immunization processes.
Non-glycosylated M. tuberculosis polypeptide vaccine composition
A vaccine comprising a non-glycosylated M. tuberculosis polypeptide Rv1324 alone or in combination with polypeptides Ag85A, Ag85B, MPT-64, Pst-S1, Apa, GroES, GroEL, Dnak, CFP10 and an adjuvant.
Use of recombinant and fusion peptide vaccines
The polypeptides can be recombinant, include purification tags, or be expressed as fusion peptides, particularly combining Apa with non-glycosylated Rv1324.
Adjuvant and emulsification agents in vaccine formulation
The inclusion of an adjuvant selected from a broad group (including DDA, MPL, aluminum salts, CpG oligonucleotides, nanoparticles, and others) and emulsification or encapsulating agents such as supramolecular biovectors, nanoparticles, or liposomes.
Pharmaceutical package comprising polypeptide vaccine and BCG vaccine
A pharmaceutical package containing the vaccine alone or combined with BCG, emulsification agents, and adjuvants as described.
Process of immunization using prime-boost strategies
A method of creating an immune response by administering the vaccine to a subject, optionally followed by administration of a second vaccine, which may be the same vaccine or BCG, in any order or simultaneously, including after exposure to M. tuberculosis.
The independent claims cover vaccines comprising specific non-glycosylated M. tuberculosis polypeptides with adjuvants and emulsifying agents, pharmaceutical packages combining these vaccines with BCG, and methods of immunization using these compositions in varied prime-boost strategies.
Stated Advantages
The vaccine increases immunoprotection against M. tuberculosis, enhancing immune response when used alone or in conjunction with the BCG vaccine.
Multi-component vaccines demonstrate synergistic immunogenicity, providing stronger immune responses than individual components.
Intranasal administration induces strong lung and mucosal immune responses, which is advantageous for protection against respiratory tuberculosis infection.
Use of non-glycosylated polypeptides produced in E. coli unexpectedly yields robust immunogenicity, offering advantages in vaccine production and efficacy.
Documented Applications
Prevention or elimination of tuberculosis disease in subjects, including as prophylactic, post-infection, or therapeutic vaccine.
Use as a standalone vaccine, priming vaccine, or boosting vaccine in prime-boost immunization strategies combined with the BCG vaccine.
Vaccination via various routes including intranasal, intradermal, subcutaneous, intramuscular, aerosolized, oral, sublingual, intravaginal, per-rectal, intravenous, and intramucosal.
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