Variation Biotechnologies Inc.

The Brigham and Women's Hospital, Inc.

Sorbonne Université

David E Anderson

Anne-Catherine Fluckiger

Andrei Ogrel

Jasminka Bozic

Marc J Kirchmeier

Tanvir Ahmed

Barthelemy Ontsouka

Francisco Diaz-Mitoma

Marc Kirchmeier

David Klatzmann

Vijay K Kuchroo

David A Hafler

Hoang-Thanh Le

José Vidal Torres

Ronald Erwin Boch

Yvonne Perrie

Mohamed Oukka

Franscisco J Diaz-Mitoma

Jose V Torres

Jeff Baxter

Mohammed Oukka

Estelle Bettelli

Charlotte Dalba-Fribert

Thanh Le

Jitinder Singh Wilkhu

The present disclosure provides compositions and methods useful for treating HCMV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCMV epitopes, such as, for example, from HCMV envelope glycoproteins gB and/or gH and/or tegument protein pp65. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation).

Compositions and methods for treatment of cytomegalovirus

The present disclosure provides compositions and methods useful for inducing a The cell response in a subject suffering from Hepatitis B. As described herein, the compositions of the disclosure comprise HBsAg having S, Pre-S1 and Pre-S2 proteins and an aluminum phosphate adjuvant. In a preferred embodiment, the immunogenic composition comprises at least 20 μg/ml of HBsAg antigen and the amount of non-adsorbed antigen is at least 30%.

Immunogenic compositions for treatment of Hepatitis B

The present disclosure provides compositions and methods useful for preventing and/or treating coronavirus infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more coronavirus epitopes, such as, for example, from SARS-Cov-2 spike protein.

Vaccine compositions for the treatment of coronavirus

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an inactivated virus in combination with a non-ionic surfactant vesicle (NISV). In certain embodiments at least a portion of the antigen present in the composition is physically associated with the NISV. In certain embodiments the compositions are lyophilized and subsequently rehydrated after a period of storage. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV. In certain embodiments the lyophilized compositions are stored at temperatures in excess of 8&#xb0; C. prior to rehydration. In certain embodiments, the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV and that were also stored at temperatures in excess of 8&#xb0; C. prior to rehydration. In certain embodiments the antigen is taken from a licensed vaccine and the administered dose of antigen is less than the standard human dose for the licensed vaccine.

Compositions and methods for treating viral infections

The present disclosure provides inter alia compositions that comprise therapeutic agents (e.g., live attenuated viral antigens, therapeutic proteins, etc.) and a lipid component. The lipid component may comprise or consist of different types of lipid or lipids as described herein. In some embodiments the therapeutic agents are thermolabile. The present disclosure also provides methods for preparing compositions, including the aforementioned compositions (e.g., melt methods and spray injection methods among others).

Methods and compositions for therapeutic agents

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an attenuated or inactivated virus in combination with a non-ionic surfactant vesicle (NISV).

The present disclosure provides compositions and methods useful for preventing and treating Zika virus infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more Zika epitopes, such as, for example, from Zika envelope glycoprotein E and the Zika structural protein NS1 including variants thereof.

Vaccine compositions for treatment of Zika virus

The present disclosure provides methods useful for determining levels of HCMV infection in host cells and, by extension, determining levels of neutralizing antibodies present in a sample. The present disclosure encompasses the recognition that HCMV viruses that have a fluorescent moiety permit detection of viral infection (e.g., by assessing fluorescence in cells after contacting the host cell with the virus). In some embodiments, levels of HCMV infection are determined by fluorescence detection where the virus has been preincubated with a test sample (e.g., a serum sample) from a subject. In some embodiments, the subject has been administered a candidate HCMV vaccine.

Methods for detection of anti-cytomegalovirus neutralizing antibodies

The present disclosure provides methods for preparing vesicles. In general, these methods include steps of providing a lyophilized lipid product and rehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. The lyophilized lipid product is prepared by dissolving vesicle-forming lipids in a polar-protic water-miscible organic solvent to produce a lipid solution and then lyophilizing the lipid solution. The present disclosure also provides antigen-containing vesicle formulations prepared using these methods. The present disclosure also provides kits that include a lyophilized lipid product in a first container and an aqueous solution comprising an antigen in a second container.

Methods for preparing vesicles and formulations produced therefrom

The present disclosure provides methods for preparing vesicles. In some embodiments, the methods involve providing a molten mixture of vesicle forming lipids and then adding the molten mixture to an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. In other embodiments, the methods involve providing a lyophilized lipid product and rehydrating the lyophilized lipid product with an aqueous solution comprising an antigen such that antigen-containing vesicles are formed. The lyophilized lipid product is prepared by melting vesicle-forming lipids to produce a molten lipid mixture and then lyophilizing the molten lipid mixture. The present disclosure also provides antigen-containing vesicle formulations prepared using these methods. The present disclosure also provides kits that include a lyophilized lipid product in a first container and an aqueous solution comprising an antigen in a second container.

The embodiments provide for the modulation of both the differentiation and activity of human T17 cells. More specifically, human T17 cell differentiation can modulated by TGF-&#x3b2; and IL-21, and their agonists and antagonists. Function of T17 cells can be modulated by, for example, BLT1 or podoplanin, and their agonists and antagonists. Additionally, the embodiments provide for the identification of T17 cells. More specifically, human T17 cells specifically upregulate BLT1 and podoplanin.

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Boston, MA, United States of America

David E Anderson