# US 9,119,815 B2 · Combined measles-malaria vaccine

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- Number: US 9,119,815 B2
- Document ID: US9119815B2
- Status: Granted
- Kind: B2
- Application number: 13/318,701
- Filed: 2010-05-03
- Published: 2012-05-17
- Granted: 2015-09-01
- Earliest claimed: 2009-05-05
- Assignees: Cadila Healthcare Limited
- Applicants: Reinhard Glueck; Agata Fazio; Viviana Giannino; Martin A Billeter
- Inventors: Reinhard Glueck; Agata Fazio; Viviana Giannino; Martin A Billeter
- Web page: https://patentgrep.com/patent/US9119815B2

## CPC

- A61K 39/165: Mumps or measles virus
- A61K 38/2013: {IL-2}
- A61K 39/0015: {Combination vaccines based on measles-mumps-rubella}
- A61K 39/015: Hemosporidia antigens, e.g. Plasmodium antigens
- A61K 39/12: Viral antigens
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/22: for herpes viruses
- A61P 33/06: Antimalarials
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 35/13: Tumour cells, irrespective of tissue of origin (tumour vaccines A61K39/00)
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- A61K 2039/55588: {Adjuvants of undefined constitution}
- A61K 2039/575: {humoral response}
- A61K 2039/70: {Multivalent vaccine}
- C12N 2760/18421: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2760/18434: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/18442: virus or viral particle as vehicle, e.g. encapsulating small organic molecule
- C12N 2760/18443: viral genome or elements thereof as genetic vector
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

A combined measles-malaria vaccine containing different attenuated recombinant measles-malaria vectors comprising a heterologous nucleic acid encoding several Plasmodium falciparum antigens is described. Preferably, it relates to viral vectors that comprise nucleic acids encoding the circumsporozoite (CS) protein of P. falciparum, the merozoite surface protein 1 (MSP-1) of P. falciparum, and its derivatives (p-42; p-83-30-38) in its glycosylated and secreted forms, and apical membrane antigen1 (AMA1) of P. falciparum, in its anchored or secreted form. The viral vector stems from an attenuated measles virus, based on a strain that is used as a vaccine and is efficient in delivering the gene of interest and that binds to and infects the relevant immune cells efficiently.

## Claims

### Claim 1

A combined measles-malaria immunogenic composition comprising a recombinant measles vaccine virus which expresses MSP1 malaria antigens and measles antigens capable of eliciting immune response against measles and malaria wherein the nucleotide sequence of MSP1 malaria antigen is selected from SEQ ID NO:7 and SEQ ID NO:8.

### Claim 2 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein the recombinant measles vaccine virus expresses single or different malaria antigens.

### Claim 3 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein the recombinant measles vaccine virus expresses MSP1 malaria antigen in both anchored and secreted forms.

### Claim 4 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein the recombinant measles vaccine virus expresses MSP1 malaria antigen in both anchored and secreted forms 3D7 strain and MAD 20.

### Claim 5 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein the recombinant measles vaccine virus expresses MSP1 malaria antigen in both anchored and secreted forms FCB1 strain.

### Claim 6 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein the recombinant measles vaccine virus expresses at least one of Diversity Covering (DiCo) AMA1 malaria antigen, DiCo-1 of AMA1 malaria antigen, DiCo-2 of AMA1 malaria antigen and DiCo-3 of AMA1 malaria antigen.

### Claim 7 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein the recombinant measles vaccine virus expresses DiCo-1, DiCo-2 and DiCo-3 of AMA1 malaria antigen.

### Claim 8 (depends on 6)

The combined measles-malaria immunogenic composition as claimed in claim 6 wherein the recombinant measles vaccine virus expresses Diversity Covering (DiCo) of AMA1 malaria antigen in trans membrane and secreted forms.

### Claim 9 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein the recombinant measles vaccine virus expresses CS malaria antigen.

### Claim 10 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein the malaria antigen is cloned between P and M or H and L protein of recombinant measles vaccine virus.

### Claim 11

A measles vaccine virus vector comprising the nucleotide sequence of an antigen of malaria wherein the nucleotide sequence is selected from SEQ ID NO:3 to SEQ ID NO:12.

### Claim 12

A measles vaccine virus vector comprising the nucleotide sequence of an antigen of malaria, wherein the measles vaccine virus vector further comprises the nucleotide sequence selected from SEQ ID NO:1 and SEQ ID NO:2.

### Claim 13 (depends on 11)

The vector as claimed in claim 11 wherein the nucleotide sequence encodes malaria antigens selected from d83-30-38 and d42 and d190 fragments of MSP1 or Diversity Covering (DiCo) AMA1 or CS protein.

### Claim 14 (depends on 11)

A host comprising the vector of claim 11.

### Claim 15 (depends on 14)

The host as claimed in claim 14 is selected from E. coli or mammalian cell line.

### Claim 16 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein the recombinant measles virus originates from a vaccine strain derived from Edmoston Zagreb.

### Claim 17

A combined measles-malaria immunogenic composition comprising a recombinant measles vaccine virus which expresses MSP1 malaria antigens and measles antigens capable of eliciting immune response against measles and malaria, wherein recombinant measles vaccine virus comprises the following sequences:
MSP-1 d-190-3D7 SEQ ID NO:3
MSP-1 d-190*-3D7 SEQ ID NO:4
MSP-1 d-83-30-38-3D7 SEQ ID NO:5
MSP-1 d-83-30-38*-3D7 SEQ ID NO:6
MSP-1 d-42-3D7 SEQ ID NO:7
MSP-1 d-42*-3D7 SEQ ID NO:8
MSP-1 d-190-FCB1 SEQ ID NO:9
CS SEQ ID NO:10
DiCo1-complete SEQ ID NO:11
DiCo1-ecto and SEQ ID NO:12.

### Claim 18 (depends on 1)

The combined measles-malaria immunogenic composition as claimed in claim 1 wherein recombinant measles vaccine virus further encoding a protein with adjuvantic properties.

### Claim 19 (depends on 1)

The immunogenic composition as claimed in claim 1 further comprising an interleukin.

### Claim 20 (depends on 1)

The immunogenic composition as claimed in claim 1 which comprises one of the described recombinant measles malaria viruses or a mixture of two to several such viruses.

### Claim 21 (depends on 1)

The immunogenic composition as claimed in claim 1 wherein the described recombinant measles malaria viruses or a mixture of two to several such viruses devoid of defective interfering particles (DIs).

### Claim 22 (depends on 1)

The immunogenic composition as claimed in claim 1 wherein the adventitiously arisen DI particles have been eliminated by plaque purification, by end point dilution or differential centrifugation.

### Claim 23 (depends on 1)

The immunogenic composition as claimed in claim 1 being a component of a combined vaccine where the other components are rubella, mumps, varicella or another live attenuated vaccine virus, naturally attenuated or recombinant, alone or in combination.

### Claim 24 (depends on 1)

The immunogenic composition as claimed in claim 1 for parenteral administration comprising a suitable stabilizer.

### Claim 25 (depends on 1)

The immunogenic composition as claimed in claim 1 comprising a suitable stabilizer, adjuvant or a combination thereof wherein the stabilizer and adjuvant are such that the vaccine can be administered parenterally, intranasally, by inhalation, orally, transdermally or in a suppository.

### Claim 26 (depends on 1)

A composition comprising the combined measles-malaria immunogenic composition as claimed in claim 1 comprising stabilizer and/or adjuvant.

### Claim 27 (depends on 19)

The immunogenic composition as claimed in claim 19 wherein the interleukin is interleukin 2.

### Claim 28 (depends on 24)

The immunogenic composition according to claim 24 wherein the stabilizer is gelatin, human serum, albumin, sorbital or a combination thereof.