JP-7854986-B2 - Vaccine composition for mucosal immune response

Inventors

• スン－シオン， パトリック
• ガビッチュ，エリザベス
• ペイコフ，ヴィクター

Assignees

• ナント ホールディングス アイピー，エルエルシー
• ナントセル，インコーポレーテッド

Dates

Publication Date

20260507

Application Date

20211022

Priority Date

20201023

Claims (15)

1. A composition comprising a freeze-dried adenovirus vector and an excipient containing aragonite , wherein the adenovirus vector comprises a nucleic acid molecule encoding at least a portion of a heterologous protein, and the adenovirus vector has a residual moisture content of less than 5% .
2. The composition according to claim 1, wherein the adenovirus vector is derived from adenovirus type 5, and the adenovirus has deletions in the E1, E2b, and E3 regions.
3. The composition according to claim 1 or 2, wherein the heterologous protein is derived from a virus.
4. The composition according to claim 3, wherein the heterologous protein is derived from a virus selected from the group consisting of SARS-CoV-2, MERS-CoV, SARS-CoV, HCoV-NL63, HCoV-229E, HCoV-OC43, HKU1, and influenza virus.
5. The composition according to claim 4, wherein the heterologous protein is derived from SARS-CoV-2.
6. The composition according to claim 5, wherein the heterogeneous protein is a spike (S) protein, a nucleocapsid (N) protein, or a membrane (M) protein.
7. The composition according to claim 6, wherein the heterogeneous protein is at least 80%, optionally at least 85%, optionally at least 90%, optionally at least 95%, optionally at least 97%, or further 100% identical to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.
8. The adenovirus vector has a residual moisture content of 0.5% to 5% as described in any one of claims 1 to 7.
9. The composition according to claim 8 , wherein the adenovirus vector has a residual moisture content of less than 3%.
10. The composition according to any one of claims 1 to 9, wherein the excipient comprises one or more compounds selected from the group consisting of lactose, sucrose, magnesium stearate, glucose, mannitol, sorbitol, starch, dextrose, maltodextrin, maltitol , and plant cellulose.
11. The composition according to any one of claims 1 to 10, wherein the excipient lacks one or more compounds selected from the group consisting of lactose, sucrose, magnesium stearate, glucose, mannitol, sorbitol, starch, dextrose, maltodextrin, maltitol , and plant cellulose.
12. A composition according to any one of claims 1 to 11 , comprising one or more compounds selected from the group consisting of sodium chloride, potassium chloride, sodium citrate, sodium phosphate, sucrose, dimethylglycine, glycine, methylsulfonylmethane, and yeast lysate.
13. A capsule comprising the composition according to any one of claims 1 to 12 .
14. The capsule according to claim 13 , which is enterically coated.
15. A capsule according to claim 13 or 14, comprising alginate.

Description

This application, with respect to the cross-reference of related applications , claims priority to U.S. Provisional Patent Application No. 63/104,770, filed on 23 October 2020, and U.S. Provisional Patent Application No. 63/082,907, filed on 24 September 2020, under Section 119(e) of the U.S. Patent Act, each of which is incorporated herein by reference. This disclosure generally relates to the field of vaccine compositions. In particular, this disclosure relates to vaccine compositions with improved stability and ease of administration, and to solid dosage forms of vaccines for efficient administration and manufacture. This application includes references to amino acid sequences and/or nucleic acid sequences, submitted concurrently with this specification as a sequence listing text file “8774-16-PCT_Sequence_Listing_ST25.txt”, file size 30,000 bytes(B), created on 22 October 2021. The aforementioned sequence listing is incorporated herein by reference in its entirety in accordance with Section 1.52(e)(5) of the U.S. Patent Law Enforcement Rules. Vaccines can be produced by leaving a culture to stand, thereby attenuating the virulence of infectious microorganisms. However, modern recombinant technology is now being used to produce viral vectors that produce antigenic proteins and can express these antigenic proteins against various infectious microorganisms. Regardless of the methods or technologies used to manufacture vaccines, a persistent challenge is the ability to store vaccines while maintaining their efficacy. Currently, a crucial part of maintaining vaccine efficacy relies on expensive refrigeration systems. To reduce the need for such costly supply chains, manufacturers have attempted to add chemical stabilizers to vaccines. However, such excipients are often toxic and can trigger allergic reactions. Vaccination protocols have problems not only with stability but also with delivery routes. Many vaccines are administered by injection, which is not preferred by many people. Vaccines are traditionally delivered by intramuscular, intradermal, or subcutaneous injection. While these injections can induce a potent systemic immune response, their effectiveness in inducing mucosal immune responses varies, and is often weak or undetectable, particularly for subunit vaccines. Antibodies produced by antigen-specific cytotoxic T cells (CTLs) and B cells can migrate from the influx-region lymph nodes treated with the injected vaccine to various organs of the body; however, their migration to various mucosal tissues (e.g., genital, intestinal, respiratory) is often limited or impossible due to inadequate homing mucosal receptors and chemotaxis. However, the intranasal route, also considered a parenteral immunization pathway, can induce a good mucosal immune response in the respiratory, genital, and intestinal tracts, which share several interconnections, and this is more achievable when the vaccine is delivered to a mucosal site. Therefore, such parenteral vaccines can, in some cases, provide protection against mucosal pathogens. Most pathogens (e.g., COVID-19) enter the body through mucosal tissues (oral cavity, respiratory tract, genital tract, and intestinal tract), and since many pathogens replicate only in mucosal tissues, mucosal vaccination can optimally induce first-line protection by inducing both innate immune responses (e.g., NK cells) and adaptive immune responses (T cells and B cells) at local and distal mucosal sites. Even considering the currently approved COVID-19 vaccines, rapid and global distribution and administration of vaccines remains challenging. Global immunization has not yet been achieved with currently approved vaccines due to numerous factors, including manufacturing and/or storage costs and other requirements. Mucosal vaccine delivery (via the buccal, sublingual, nasal, oral, or vaginal mucosa) is gaining increasing interest as a means of inducing local and distal antibody-immune responses as well as systemic immune responses. In addition, mucosal vaccine delivery in solid dosage forms (e.g., buccal/sublingual tablets, oral tablets or capsules, vaginal inserts) can offer several advantages, including the potential for herd immunization, patient compliance, ease of use, product shelf-life stability, and cold-chain-independent performance. Furthermore, mucosal vaccine delivery may be suitable for patients with needle phobia, who can self-administer the vaccine after receiving appropriate instructions. While the buccal/sublingual route has been used for many years to deliver drugs and small molecules into the bloodstream, its application as a means of mucosal vaccine delivery has not been conventionally developed. Solid dosage forms for drug delivery, including powders, tablets, or capsules, require disintegration and release of the active ingredient (e.g., vaccine) upon administration. Simultaneously, the dosage form containing the active ingredient must remain stable during transport