COMPOSITIONS FOR USE IN TREATMENT OF ACNE

1 . A nucleic acid comprising a nucleotide sequence encoding a modified Cutibacterium acnes ( C. acnes ) Christie-Atkins-Munch-Petersen factor 2 (CAMP2) polypeptide, wherein the modified C. acnes CAMP2 polypeptide comprises an amino acid sequence comprising a C. acnes CAMP2 polypeptide sequence and a transmembrane domain sequence.

2 . The nucleic acid of claim 1 , wherein:

(A) (a) the transmembrane domain sequence is positioned at the C terminus of the modified C. acnes CAMP2 polypeptide; and/or

(b) the transmembrane domain sequence comprises a viral transmembrane domain sequence, which is optionally selected from the group consisting of: an influenza hemagglutinin (HA) transmembrane domain sequence, a SARS CoV-2 spike transmembrane domain sequence, a VZV gB transmembrane domain sequence, a VZV gE transmembrane domain sequence, a VZV gI transmembrane domain sequence, a VZV gK transmembrane domain sequence, a measles F-protein transmembrane domain sequence, a rubella E1 protein transmembrane domain sequence, a rubella E2 protein transmembrane domain sequence, a mumps F-protein transmembrane domain sequence, an Ebola GP protein transmembrane domain sequence and a rabies transmembrane domain sequence, optionally wherein the transmembrane domain comprises an amino acid sequence selected from the group consisting of sequences set forth by SEQ ID NO: 208-209 and 241-253; and/or

(B) the modified C. acnes CAMP2 polypeptide comprises a non-native secretion signal peptide sequence (e.g., a viral secretion signal peptide sequence), optionally wherein:

(a) the secretion signal peptide sequence is positioned at the N terminus of the modified C. acnes CAMP2 polypeptide; and/or

(b) the secretion signal peptide sequence is a viral secretion signal peptide sequence, which is optionally selected from the group consisting of: an influenza hemagglutinin (HA) secretion signal peptide sequence, a SARS CoV-2 spike secretion signal peptide sequence, a VZV gB secretion signal peptide sequence, a VZV gE secretion signal peptide sequence, a VZV gI secretion signal peptide sequence, a VZV gK secretion signal peptide sequence, a measles F-protein secretion signal peptide sequence, a rubella E1 protein secretion signal peptide sequence, a rubella E2 protein secretion signal peptide sequence, a mumps F-protein secretion signal peptide sequence, an Ebola GP protein secretion signal peptide sequence, a smallpox 6 kDa IC protein secretion signal peptide sequence and a rabies G protein secretion signal peptide sequence, e.g., wherein the secretion signal peptide sequence comprises a sequence selected from the group consisting of sequences set forth by SEQ ID NO: 208-209 and 241-253; and/or

wherein the nucleic acid is a messenger RNA (mRNA), optionally wherein

(a) the mRNA comprises a 5′ cap, at least one 5′ untranslated region (5′ UTR), at least one 3′ untranslated region (3′ UTR), and/or at least one polyadenylation (poly(A)) sequence;

(b) the mRNA is unmodified or comprises at least one chemical modification, optionally wherein the mRNA comprises at least one chemical modification, e.g., wherein the chemical modification comprises N1-methylpseudouridine; and/or

(c) the mRNA is a self-replicating mRNA or a non-replicating mRNA.

3 . (canceled)

4 . (canceled)

5 . The nucleic acid of claim 1 , wherein:

(a) the modified C. acnes CAMP2 polypeptide comprises a sequence according to any one of SEQ ID NO: 207 or SEQ ID NO: 5-9, or a sequence having at least 60% identity thereto; and/or

(b) the nucleic acid comprises a nucleotide sequence according to any one of SEQ ID NO: 90-94 or SEQ ID NO: 391-392, or a sequence having at least 50% identity thereto; and/or

(c) the nucleic acid is a mRNA comprising or consisting of the following structural elements:

(i) a 5′ cap with the following structure:

(ii) a 5′ untranslated region (5′ UTR) having the nucleic acid sequence according to SEQ ID NO: 265;

(iii) a protein coding region having the nucleic acid sequence according to any one of SEQ ID NO: 90-91 or SEQ ID NO: 391-392 (e.g., SEQ ID NO: 91);

(iv) a 3′ untranslated region (3′ UTR) having the nucleic acid sequence according to SEQ ID NO: 266; and

(v) a polyA tail, optionally wherein the poly A tail comprises at least 75 adenosine nucleotides or at least 100 adenosine nucleotides.

6 . (canceled)

7 . A modified C. acnes CAMP2 polypeptide having an amino acid sequence comprising a C. acnes CAMP2 polypeptide sequence and a transmembrane domain sequence.

8 . The modified C. acnes CAMP2 polypeptide of claim 7 , wherein:

(A) the transmembrane domain sequence is positioned at the C-terminus of the modified C. acnes CAMP2 polypeptide; and/or

(B) the transmembrane domain comprises a viral transmembrane domain sequence, which is optionally selected from the group consisting of: an influenza hemagglutinin (HA) transmembrane domain sequence, a SARS CoV-2 spike transmembrane domain sequence, a VZV gB transmembrane domain sequence, a VZV gE transmembrane domain sequence, a VZV gI transmembrane domain sequence, a VZV gK transmembrane domain sequence, a measles F-protein transmembrane domain sequence, a rubella E1 protein transmembrane domain sequence, a rubella E2 protein transmembrane domain sequence, a mumps F-protein transmembrane domain sequence, an Ebola GP protein transmembrane domain sequence and a rabies transmembrane domain sequence, e.g. wherein the transmembrane domain comprises an amino acid sequence selected from the group consisting of sequences set forth by SEQ ID NO: 208-209 and 241-253; and/or

(C) the modified C. acnes CAMP2 polypeptide comprises a sequence according to any one of SEQ ID NO: 207 or SEQ ID NO: 5-9, or a sequence having at least 60% identity thereto.

9 . (canceled)

10 . A composition comprising:

(a) the nucleic acid of claim 1 , optionally wherein the composition is an immunogenic composition;

(b) a nucleic acid comprising a nucleotide sequence encoding a C. acnes CAMP2 polypeptide, wherein the nucleic acid is a mRNA, and wherein the composition is an immunogenic composition; or

(c) a nucleic acid comprising a nucleotide sequence encoding a C. acnes CAMP2 polypeptide and one or more of:

(i) a nucleic acid comprising a nucleotide sequence encoding a C. acnes dermatan sulfate-adhesin 1 (DsA1) polypeptide;

(ii) a nucleic acid comprising a nucleotide sequence encoding a C. acnes dermatan sulfate-adhesin 2 (DsA2) polypeptide;

(iii) a nucleic acid comprising a nucleotide sequence encoding a C. acnes putative iron-transport protein (PITP) polypeptide;

(iv) a nucleic acid comprising a nucleotide sequence encoding a chimeric C. acnes DsA1/DsA2 polypeptide; and

(v) a nucleic acid comprising a nucleotide sequence encoding a chimeric C. acnes DsA1/DsA2/PITP polypeptide;

optionally wherein the composition according to (c) is an immunogenic composition, further optionally wherein the composition according to any one of (a)-(c) is in a frozen liquid form or in a lyophilized form (e.g., in a lyophilized form).

11 . The composition of claim 10 (c), wherein the composition comprises the nucleic acid according to (c) (iii) and/or the nucleic acid according to (c) (iv), optionally wherein:

(A) the C. acnes CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 203 or a sequence having at least 60% (e.g., at least 85%) identity thereto;

(B) the chimeric C. acnes DsA1/DsA2 polypeptide comprises a sequence according to SEQ ID NO: 70 or a sequence having at least 90% identity thereto; and

(C) the C. acnes PITP polypeptide comprises a sequence according to SEQ ID NO: 73 or a sequence having at least 75% identity thereto.

12 . The composition of claim 10 , wherein the composition is as defined in claim 10 (a) or (b), and wherein the composition further comprises one or more of:

(i) a nucleic acid comprising a nucleotide sequence encoding a C. acnes DsA1 polypeptide;

(ii) a nucleic acid comprising a nucleotide sequence encoding a C. acnes DsA2 polypeptide;

(iii) a nucleic acid comprising a nucleotide sequence encoding a C. acnes PITP polypeptide;

(iv) a nucleic acid comprising a nucleotide sequence encoding a chimeric C. acnes DsA1/DsA2 polypeptide; and

(v) a nucleic acid comprising a nucleotide sequence encoding a chimeric C. acnes DsA1/DsA2/PITP polypeptide, optionally wherein:

the composition comprises the nucleic acid according to (iii) and/or the nucleic acid according to (iv), optionally wherein:

(A) the C. acnes CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 207 or a sequence having at least 60% identity thereto; the chimeric C. acnes DsA1/DsA2 polypeptide comprises a sequence according to SEQ ID NO: 70 or a sequence having at least 90% identity thereto; and the C. acnes PITP polypeptide comprises a sequence according to SEQ ID NO: 73 or a sequence having at least 75% identity thereto; and/or

(B) the nucleotide sequence encoding the C. acnes CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 91 or a sequence having at least 50% identity thereto; the nucleotide sequence encoding the chimeric C. acnes DsA1/DsA2 polypeptide comprises a sequence according to SEQ ID NO: 113 or a sequence having at least 75% identity thereto; and the nucleotide sequence encoding the C. acnes PITP polypeptide comprises a sequence according to SEQ ID NO: 115 or a sequence having at least 50% identity thereto.

13 - 15 . (canceled)

16 . The composition of claim 10 , wherein the composition comprises:

(A) a first mRNA comprising or consisting of the following structural elements:

(i) a 5′ cap;

(ii) a 5′ UTR having the nucleic acid sequence according to SEQ ID NO: 265;

(iii) a protein coding region having the nucleic acid sequence according to SEQ ID NO: 91;

(iv) a 3′ UTR having the nucleic acid sequence according to SEQ ID NO: 266; and

(v) a polyA tail, optionally wherein the polyA tail comprises at least 75 adenosine nucleotides or at least 100 adenosine nucleotides;

(B) a second mRNA comprising or consisting of the following structural elements:

(i) a 5′ cap;

(ii) a 5′ UTR having the nucleic acid sequence according to SEQ ID NO: 265;

(iii) a protein coding region having the nucleic acid sequence according to SEQ ID NO: 113;

(iv) a 3′ UTR having the nucleic acid sequence according to SEQ ID NO: 266; and

(v) a polyA tail, optionally wherein the polyA tail comprises at least 75 adenosine nucleotides or at least 100 adenosine nucleotides; and

(C) a third mRNA comprising or consisting of the following structural elements:

(i) a 5′ cap;

(ii) a 5′ UTR having the nucleic acid sequence according to SEQ ID NO: 265;

(iii) a protein coding region having the nucleic acid sequence according to SEQ ID NO: 115;

(iv) a 3′ UTR having the nucleic acid sequence according to SEQ ID NO: 266; and

(v) a polyA tail, optionally wherein the polyA tail comprises at least 75 adenosine nucleotides or at least 100 adenosine nucleotides;

wherein the 5′ cap has the following structure:

and optionally wherein one or more of the first, second and third mRNAs comprises at least one chemical modification.

17 . (canceled)

18 . The composition of claim 10 , wherein the composition further comprises a lipid nanoparticle (LNP), optionally wherein:

(a) any one or more nucleic acids are encapsulated in the LNP;

(b) any two or more nucleic acids are co-encapsulated in a single LNP; and/or

(c) any two or more nucleic acids are encapsulated in separate LNPs, optionally wherein:

the LNP comprises at least one cationic lipid and wherein the cationic lipid is selected from the group consisting of OF-02, cKK-E10, IM-001, IS-001 and GL-HEPES-E3-E12-DS-4-E10, preferably wherein the cationic lipid is GL-HEPES-E3-E12-DS-4-E10; and/or

the LNP further comprises a polyethylene glycol (PEG) conjugated (PEGylated) lipid, a cholesterol-based lipid, and a helper lipid; and/or

the LNP comprises GL-HEPES-E3-E12-DS-4-E10 at a molar ratio of 35% to 55%;

DMG-PEG2000 at a molar ratio of 0.25% to 2.75%; cholesterol at a molar ratio of 20% to 50%; and DOPE at a molar ratio of 5% to 35%; and/or

the LNP comprises GL-HEPES-E3-E12-DS-4-E10 at a molar ratio of 40%, DMG-PEG2000 at a molar ratio of 1.5%, cholesterol at a molar ratio of 28.5% and DOPE at a molar ratio of 30%.

19 - 22 . (canceled)

23 . A composition, optionally an immunogenic composition, comprising:

the modified C. acnes CAMP2 polypeptide of claim 7 .

24 . The composition of claim 23 , wherein the composition further comprises one or more of:

(A) a C. acnes DsA1 polypeptide,

(B) a C. acnes DsA2 polypeptide,

(C) a C. acnes PITP polypeptide,

(D) a chimeric C. acnes DsA1/DsA2 polypeptide, and

(E) a chimeric C. acnes DsA1/DsA2/PITP polypeptide.

25 . The composition of claim 10 , wherein the C. acnes CAMP2 polypeptide, the C. acnes DsA1 polypeptide, the C. acnes DsA2 polypeptide, the C. acnes PITP polypeptide, the chimeric C. acnes DsA1/DsA2 polypeptide, and the chimeric C. acnes DsA1/DsA2/PITP polypeptide further comprise a non-native transmembrane domain sequence and/or a non-native secretion signal peptide sequence.

26 . The composition of claim 10 , wherein:

(a) one or more of the C. acnes CAMP2 polypeptide, the C. acnes DsA1 polypeptide, the C. acnes DsA2 polypeptide, the C. acnes PITP polypeptide, the chimeric C. acnes DsA1/DsA2 polypeptide and the chimeric C. acnes DsA1/DsA2/PITP polypeptide comprises a mutation at one or more (e.g., all) positions corresponding to an N-glycosylation site and/or one or more (e.g., all) positions corresponding to an O-glycosylation site in the respective native C. acnes polypeptide, optionally wherein the mutation is a single amino acid substitution; and/or

(b) one or more of the C. acnes DsA1 polypeptide, the C. acnes DsA2 polypeptide, the C. acnes PITP polypeptide, the chimeric C. acnes DsA1/DsA2 polypeptide and the chimeric C. acnes DsA1/DsA2/PITP polypeptide comprises a single amino acid substitution at one or more (e.g., all) positions corresponding to a cysteine residue in the respective native C. acnes polypeptide, optionally wherein the single amino acid substitution is a substitution of cysteine with serine.

27 . The composition of claim 10 , wherein:

(a) the C. acnes CAMP2 polypeptide comprises a sequence according to any one of SEQ ID NO: 203, SEQ ID NO: 43-58, SEQ ID NO: 1-4, SEQ ID NO: 10-16 or SEQ ID NO: 339-363 or a sequence having at least 60% identity thereto;

(b) the C. acnes DsA1 polypeptide comprises a sequence according to any one of SEQ ID NO: 204 or SEQ ID NO: 17-19 or SEQ ID NO: 59-61, or a sequence having at least 75% identity thereto;

(c) the C. acnes DsA2 polypeptide comprises a sequence according to any one of SEQ ID NO: 205 or SEQ ID NO: 20-27 or SEQ ID NO: 62-69 or a sequence having at least 75% identity thereto;

(d) the C. acnes PITP polypeptide comprises a sequence according to any one of SEQ ID NO: 206, SEQ ID NO: 31-37, SEQ ID NO: 73-79 or a sequence having at least 75% (e.g. 90 or 95%) identity thereto;

(e) the chimeric C. acnes DsA1/DsA2 polypeptide comprises a sequence according to any one of SEQ ID NO: 28-30, SEQ ID NO: 39 or SEQ ID NO: 70-72 or SEQ ID NO: 81, or a sequence having at least 90% identity thereto; and/or

(f) the chimeric C. acnes DsA1/DsA2/PITP polypeptide comprises (i) a sequence of any one of SEQ ID NO: 28-30, SEQ ID NO: 39 or SEQ ID NO: 70-72 or SEQ ID NO: 81, or a sequence having at least 90% identity thereto; and (ii) a PITP polypeptide sequence, optionally wherein the chimeric C. acnes DsA1/DsA2/PITP polypeptide comprises a sequence according to any one of SEQ ID NO: 38, SEQ ID NO: 40-41, SEQ ID NO: 80, SEQ ID NO: 82-83, SEQ ID NO: 367-368, or a sequence having at least 90% identity thereto.

28 . The composition of claim 10 , wherein the composition comprises:

(a) a C. acnes CAMP2 polypeptide comprising or consisting of a sequence according to SEQ ID NO: 203;

(b) a chimeric C. acnes DsA1/DsA2 polypeptide comprising or consisting of a sequence according to SEQ ID NO: 70; and

(c) C. acnes PITP polypeptide comprising or consisting of a sequence according to SEQ ID NO: 73.

29 . The composition of claim 23 , wherein the composition further comprises an adjuvant, optionally wherein the adjuvant is selected from the group consisting of: aluminum based adjuvant, squalene based oil in water emulsion adjuvants and liposome-based adjuvants comprising a saponin and a TLR4 agonist, further optionally wherein the adjuvant is selected from the group consisting of AlOOH, AF03 and SPA14.

30 . A nucleic acid comprising a nucleotide sequence encoding a chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide, wherein the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises:

(a) a chimeric C. acnes DsA1/DsA2 polypeptide;

(b) an immunogenic fragment of a C. acnes PITP polypeptide, optionally wherein the immunogenic fragment comprises a ENFD of a C. acnes PITP polypeptide; and

(c) a C. acnes CAMP2 polypeptide or an immunogenic fragment thereof.

31 . A chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprising:

(a) a chimeric C. acnes DsA1/DsA2 polypeptide;

(b) an immunogenic fragment of a C. acnes PITP polypeptide, optionally wherein the immunogenic fragment comprises a ENFD of a C. acnes PITP polypeptide; and

(c) a C. acnes CAMP2 polypeptide or an immunogenic fragment thereof.

32 . The nucleic acid of claim 30 , wherein

i. the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises a first conserved sub-domain (CSD1) of a C. acnes DsA1 polypeptide, a second conserved sub-domain (CSD2) of a C. acnes DsA2 polypeptide and a third conserved sub-domain (CSD3) of a C. acnes DsA1 polypeptide, optionally wherein the chimeric C. acnes DsA1/DsA2 polypeptide of (a) comprises a sequence according to SEQ ID NO: 70, or a sequence having at least 90%, identity thereto;

ii. the immunogenic fragment of a C. acnes PITP polypeptide in (b) comprising an extended neocarzinostatin family domain (ENFD) of a C. acnes PITP polypeptide comprises the sequence corresponding to amino acid residues 1-133 or residues 1-146 of SEQ ID NO: 73 or a sequence having at least 90% identity thereto; and/or

iii. (c) is (1) a C. acnes CAMP2 polypeptide, optionally wherein (c) comprises SEQ ID NO: 203 or a sequence having at least 90% identity thereto; or (2) an immunogenic fragment of a C. acnes CAMP2 polypeptide comprising a N-terminal domain of a C. acnes CAMP2 polypeptide, e.g. wherein the immunogenic fragment comprises amino acid residues 29-176 of SEQ ID NO: 202 or a sequence having at least 90% identity to the sequence of amino acid residues 29-176 of SEQ ID NO: 202.

33 . (canceled)

34 . The nucleic acid of claim 30 , wherein:

(i) the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 374-375; or

(ii) the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 373 and a transmembrane domain sequence

optionally wherein the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 374 or wherein the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 373 and a TMB sequence according to SEQ ID NO: 84; and/or

(i) the nucleotide sequence encoding the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises a sequence according to any one of SEQ ID NO: 377-382 or 384-389; or

(ii) the nucleotide sequence encoding the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 384 and a sequence according to SEQ ID NO: 395; or a sequence according to SEQ ID NO: 385 and a sequence according to SEQ ID NO: 396,

optionally wherein the nucleotide sequence encoding the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 387 or the nucleotide sequence encoding the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide comprises a sequence according to SEQ ID NO: 385 and a sequence according to SEQ ID NO: 396.

35 - 40 . (canceled)

41 . A method of generating an immune response against a C. acnes infection in a subject or a method of treating or preventing C. acnes infection in a subject, the method comprising administering the nucleic acid of claim 1 to the subject.

42 . (canceled)

43 . The method of claim 41 , wherein the method comprises:

(i) administering one dose of the nucleic acid, the polypeptide or the composition; or

(ii) administering two doses of the nucleic acid, the polypeptide or the composition, optionally wherein the two doses are administered two months apart; and/or

the subject is a human subject and wherein the subject is between 9 and 45 years old or between 12 and 45 years old; and/or

the method comprises administering the nucleic acid intramuscularly or through skin injection.

44 . (canceled)

45 . (canceled)

46 . A method of generating an immune response against a C. acnes infection in a subject or a method of treating or preventing C. acnes infection in a subject, the method comprising administering the modified C. acnes CAMP2 polypeptide of claim 7 to the subject.

47 . A method of generating an immune response against a C. acnes infection in a subject or a method of treating or preventing C. acnes infection in a subject, the method comprising administering the composition of claim 10 to the subject.

48 . A method of generating an immune response against a C. acnes infection in a subject or a method of treating or preventing C. acnes infection in a subject, the method comprising administering the composition of claim 23 to the subject.

49 . A method of generating an immune response against a C. acnes infection in a subject or a method of treating or preventing C. acnes infection in a subject, the method comprising administering the nucleic acid of claim 30 to the subject.

50 . A method of generating an immune response against a C. acnes infection in a subject or a method of treating or preventing C. acnes infection in a subject, the method comprising administering the chimeric C. acnes DsA1/DsA2/PITP/CAMP2 polypeptide of claim 31 to the subject.

51 . A composition, optionally an immunogenic composition, comprising a C. acnes CAMP2 polypeptide and one or more of:

(i) a C. acnes DsA1 polypeptide,

(ii) a C. acnes DsA2 polypeptide,

(iii) a C. acnes PITP polypeptide,

(iv) a chimeric C. acnes DsA1/DsA2 polypeptide, and

(v) a chimeric C. acnes DsA1/DsA2/PITP polypeptide.

52 . A method of generating an immune response against a C. acnes infection in a subject or a method of treating or preventing C. acnes infection in a subject, the method comprising administering the composition of claim 51 to the subject.