Platform Technology

BioComo focuses on creating the innovative vaccine technology platforms and the predominant immunity enhancing system for infectious diseases difficult to combat and for malignant tumors resistant to conventional therapy. We have developed a novel vaccine carrier technology named as BC-PIV and a novel adjuvant candidate named as BC-A. BC-PIV is the first inactivated paramyxovirus vector carrying multiple antigens. BC-A is a novel adjuvant candidate or vaccine.

Vector Technology

1.BC-PIV vector technology (key technology)

BC-PIV is a chemically-inactivated virus system for vaccine carrier derived from the recombinant human parainfluenza virus 2 (hPIV2) vectors carrying RNA genome, intentionally/genetically incorporating a range of vaccine antigens displayed on it and eliciting strong and long-lasting humoral and cellular immune without adjuvant. Compared to VLP (virus like particle) which is a topical technology for delivery of limited peptide/protein antigens, BC-PIV has versatile peptides/proteins function adjusted to a lot of vaccine antigens. Consequently BC-PIV can demonstrate higher gene modality for infectious diseases as well as malignant tumors with better safety profile.

VLP BC-PIV
Preparation Method -express assembly-forming antigens in vacuro virus, yeast or E.coli
-collect VLP assembly
-construct recombinant hPIV2 enpressing plural antigens on the surface
-inactive the hPIV2 by original method
Strength -easy for vaccine design
-simple way for manufacturing
-no need of a large scale plant
-topical technolgy
-veesatile and long antigens avilable
-diverse administration reoute
-humoral and celllar immune induction without adjuvant
-cost effective
Example HBV:「Bimmugen」「HEPTAVAX-II、Ebr> HPVE「Cervarix」「Gardasil、Ebr> universalflu vaccine, RSV vaccine, Ebola virus vaccine, cancer vaccine

BC-PIV is characterized by the modality of antigen incorporation and the inactivation of viral genome. The incorporation of antigens is enhanced by gene-technological engineering producing peptide/protein antigens on various locations, outside, inside and out/inside of the vesicle. BioComo’s original treatment for viral inactivation has the following property: The treatment can fully inactivate the RNA genome of recombinant hPIV2 to non-replication, while the protein structure of the envelope proteins still and potentially maintain physiological and biological properties retaining immunogenicity and receptor-mediated fusogenicity like live recombinant hPIV2.



Recombinant hPIV2 is the non-transmissible and single-round infectious hPIV2 vector in a strategy for recombinant vaccine and gene therapy development. The high performance stable packaging cell line was produced to construct the master cell bank (US patent: US8,911,975B2).


2.Recombinant hPIV2 technology



Adjuvant Technology

Development of Adjuvant
We had searched for substances that can activate costimulatory molecules (such as CD80, CD40) by innate immune stimulation in dendritic cells and eventually found candidates effectively to put innate immunity to work for the adaptive immune response with/without cytokine induction.
Pipeline
Influenza virus (universal antigen M2e: highly conserved across flu subtypes)
BC-PIV harboring a large amount of M2e linked to the immunogenic carrier of HN or F envelope proteins of hPIV2 with various modalities of incorporation shown in (1) BC-PIV technology efficiently induced anti-M2e mucosal and systemic antibody responses through intranasal vaccination for IgA or intramuscular vaccination for IgG in mouse model, respectively. For evaluation of BC-PIV with M2e vaccine efficacy in higher animals such as ferrets, we plan to conduct immunogenicity and protective studies.

RSV vaccine
BC-PIV harboring RSV F antigen is a viral-genome-specific-inactivated vector, while can potentially deliver prefusion F through structure-based design targeting both seronegative infants and elderly people.
Ebola vaccine
BC-PIV/Ebola GP targeting GP protein.
BC-PIV/Ebola GP is an adroitly-inactivated vector and can have safety profile with point mutated GP blocking GP-mediated entry targeting infants through elderly people.
Malignant tumor
BC-PIV can has shown evidence leading to activation of dendritic cells and effectively initiate a dynamic process of activating the host Th-1 immune system to facilitate cross-priming and tumor-specific T-cell generation to induce immunogenic tumor cell death with equivalent efficacy of Dacarbazine (DTIC) by intradermal administration in melanoma animal model. Furthermore we believe that when used in combination with cancer vaccines, immune check inhibitors would invariably have a synergy effect on immune responses and antitumor activity. Therefore, we are mounting evidences that BC-PIV can have immunomodulatory and synergy properties that can be exploited to enhance antitumor effects of immune check inhibitors.
Adjuvant technology
Three potential adjuvant candidates are tested for in-depth properties enhancing the immunogenicity of antigens, having capacity to stimulate cellular (Th1) immune responses, reducing the amount of antigen, and improving the efficacy of vaccines in newborns or the elderly animals.

PipelineFeature
BC-PIV
(platformEE/th>
-versatile/plural antigens available(no need of antigen preparationEEbr> -intranasal, intramuscular, intradermal administration available
-humoral and cellular immune induction
-sophisticated vector inactivation(genome: no replication,envelope protein:intact)
recombinant hPIV2
(recombinant viral vector)
-therapeutic/ antigen gene available
-non-transmissible vector system
-mastercell bank
BC-A
(adjuvant)
-effective activation of dendritic cell(CD80,86,40EEbr> -enhancement of vaccine effect

Publication

1. HUMAN GENE THERAPY 24:683?691 (2013)
Title Human Parainfluenza Virus Type 2 Vector Induces Dendritic Cell Maturation Without  Viral RNA Replication/Transcription Human Parainfluenza Virus Type 2 Vector Induces Dendritic Cell Maturation Without  Viral RNA Replication/Transcription
Authors Kenichiro Hara, Masayuki Fukumura, Junpei Ohtsuka, Mitsuo Kawano, and Tetsuya Nosaka
2. Gen Ther.;21(8):775-84(2014)
Title Vero/BC-F: an efficient packaging cell line stably expressing F protein to generate single round-infectious human parainfluenza virus type 2 vector
Authors Junpei Ohtsuka, Masayuki Fukumura, Masato Tsurudome, Kenichiro Hara, Mcchiko Nishio, Mitsuo Kawano, and Tetsuya Nosaka
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