Liposome carriers for use in enhancing vaccine development
Inventors
Alving, Carl R. • Rao, Venigalla
Assignees
Catholic University of America • United States Department of the Army
Publication Number
US-8148130-B2
Publication Date
2012-04-03
Expiration Date
2028-02-29
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Abstract
T4 bacteriophages are bound to substrates such as liposomes using a binder.
Core Innovation
The invention provides compositions and methods for binding T4 bacteriophages or their derivatives to substrates such as liposomes using glucoconjugates, specifically glucosyl ceramide. This allows for the creation of complexes in which T4 bacteriophages displaying antigens, fusion proteins, or other molecules are bound to liposomes by a glucoconjugate, facilitating self-assembly of liposomal antigen formulations.
The problem addressed by the invention is the difficulty in manufacturing liposome vaccine formulations that have high immuno-stimulating capacities but are challenging to produce and have limited commercial potential. Large multilamellar liposomes, which are optimal for vaccine delivery due to their effective uptake by antigen presenting cells, cannot easily be sterilized by filtration and require sterile manufacturing conditions, making the vaccine production process awkward and inefficient.
The present invention solves these challenges by providing liposomes that contain binding sites, such as glucosyl ceramide, for T4 bacteriophages displaying antigens, enabling the formation of self-assembling nanovaccines. This approach permits antigen loading onto liposomes after liposome formation, potentially within a closed sterile environment such as an injection vial. The T4 bacteriophage serves as a versatile nanoparticle capable of displaying multiple antigens on its capsid surface or carrying antigen-encoding DNA, combined with liposomes carrying adjuvants like lipid A to enhance immune responses.
Claims Coverage
The patent includes two independent claims that focus on compositions comprising liposomes with glucoconjugates bound to T4 bacteriophage components and the specific features of these components and their binding systems.
Composition comprising liposome with glucosyl ceramide bound T4 bacteriophages
A composition including a substrate comprising a liposome and a glucoconjugate wherein the glucoconjugate is specifically glucosyl ceramide inserted into the lipid bilayer of the liposome. One or more T4 bacteriophage or T4 bacteriophage derivatives having antigens, fusion proteins, or other molecules are bound to the substrate by the glucoconjugate.
Inclusion of adjuvants and multiple antigen types on T4 bacteriophage
The composition may include an adjuvant within the substrate or liposome. There may be one or more types of antigens bound to one or more T4 bacteriophages, including two or more different types of antigens. The T4 bacteriophage may comprise Hoc and/or Soc fusion proteins, where each fusion protein consists of a foreign protein fused to Hoc or Soc, with the foreign proteins being antigenic or selected from a list of immunologically relevant proteins and molecules.
Composition comprising liposome with multiple lipid components and T4 bacteriophage derivatives
A composition comprising a liposome substrate with a glucoconjugate which is a glycolipid inserted into the liposome's lipid bilayer. The liposome includes dimyristoyl phosphatidylcholine, dimyristoyl phosphatidylglycerol, cholesterol, and lipid A. One or more T4 bacteriophage derivatives with antigens or fusion proteins bound to the liposome by the glucoconjugate.
The inventive features define compositions where T4 bacteriophages or derivatives displaying antigens are bound to liposomes via glucoconjugates, particularly glucosyl ceramide, with inclusion of adjuvants and customizable antigenic fusion proteins bound to the T4 capsid, and specific lipid compositions for the liposome substrates enabling self-assembling nanovaccine formulations.
Stated Advantages
The invention allows self-assembly of bacteriophage particles on liposome surfaces, eliminating the need to add antigen during liposome manufacture, thus enabling vaccine formulations to be prepared in closed sterile environments.
Liposome formulations with T4 bacteriophage-bound antigens show enhanced immunogenicity, including induction of strong antigen-specific antibody responses.
The system enables versatile antigen display with control over antigen types and copy numbers on the T4 capsid, potentially allowing for multicomponent and multi-epitope vaccines.
Use of glucosyl ceramide as a glucoconjugate binder enhances binding affinity between T4 bacteriophage and liposomes, improving stability and efficiency of vaccine delivery.
Documented Applications
The compositions and methods are explicitly described for use as vaccine formulations, including protein and DNA vaccines using T4 bacteriophage displaying HIV antigens or anthrax antigens.
The formulations are used for inducing immune responses in animals, such as mice and rabbits, against infectious diseases like HIV and anthrax.
The invention is applied to manufacture liposome vaccine formulations that can be prepared sterilely and self-assembled in situ.
Use in immunization methods involving intramuscular injection and evaluation of humoral and cellular immune responses, including assessment of neutralizing antibodies against HIV.
Development of nanovaccine adjuvants leveraging bacteriophage-liposome complexes to stimulate innate and adaptive immunity.
Potential application as a molecular diagnostic system exploiting displayed molecules on bacteriophage to detect pathogens or components through specific interactions.
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