Title:  Intranasal yellow fever vaccination

United States Patent:  6,337,073

Assignee:  Deutsches Primatenzentrumg GmbH (Gottingen, DE)

Filed:  June 22, 2000

PCT NO:  PCT/EP98/08387

102(e) Date:  June 22, 2000

PCT PUB. Date:  July 1, 1999

Foreign Application Priority Data:  Dec 22, 1997[DE] (197 57 301)

The invention relates to vaccine preparations, pharmaceutical preparations and methods for inducing protective immunity in humans using a live, attenuated yellow fever virus of strain D17 preferably administered by an intranasal route of administration. The inventors have also developed an assay for detecting the induction of both the binding and neutralizing antibodies formed in a protective immune response in humans who have received an intranasal vaccine preparation of the kind described.

Description of the Invention

The invention relates to a medicament preparation for intranasal vaccination against yellow fever.

Yellow fever is a serious health problem in many areas of Africa and South America. Since the introduction of the live, attenuated 17D vaccine strain against yellow fever virus infection by Theiler in 1937 a very effective vaccine, which shows virtually no side effects, has been available against this infection (Theiler et al., J. Ex. Med. 65 (1937) 787-800). Prophylactic immunization with this active substance is very effective because immunity appears to persist life-long. However, because of incomplete vaccination of the population with 17D in endemic areas, yellow fever epidemics have occurred and still occur (Robertson et al., JAMA 276, No. 14 (1996) 1157-1162). This is connected in particular with the fact that the subcutaneous yellow fever vaccination used in the state of the art involves great expenditure and thus often cannot be employed comprehensively in many countries.

One object of the invention was therefore to provide a medicament preparation for vaccination against yellow fever which can be used in a simpler form than by subcutaneous injection.

This object is achieved according to the invention by a medicament preparation for intranasal vaccination against yellow fever.

It has been found in this connection that on intranasal administration of a vaccine against yellow fever it is possible to achieve an effective immune response leading to the expectation of reliable vaccine protection.

It is possible by administering an active substance against yellow fever through the nose to obtain reliable vaccine protection which is not inferior to the vaccine protection to be achieved by subcutaneous vaccination. In contrast to this, no immune response leading to the expectation of reliable vaccine protection is achieved with other administration routes such as, for example, oral or gastrointestinal. Intranasal vaccination makes economic administration possible, which makes possible general vaccination which is simple to perform, and is thus suitable in particular for mass immunizations.

The medicament preparation according to the invention preferably comprises as active substance the yellow fever vaccine strain 17D, in particular a live, attenuated 17D yellow fever vaccine complying with the stipulations of the World Health Organization (Barry et al., "Requirements for Yellow Fever Vaccine", WHO Technical Report Series, No. 594 (1976) 34-35). A single vaccine dose preferably contains at least 10³ plaque-forming units (PFU).

The active substance is preferably introduced into a solvent suitable for intranasal administration. Examples of suitable solvents are physiological salt solutions such as, for example, a 0.9% strength sodium chloride solution. The active substance is preferably dissolved in the salt solution, for example sodium chloride solution, immediately before use. Other suitable solvents are distilled water and heavy water (D₂ O), with each of which excellent stabilization of the vaccine can be achieved. The medicament preparation according to the invention may additionally comprise other pharmaceutically suitable solvents and/or excipients. The solvent is employed in particular for dissolving and administering freeze-dried 17D vaccine.

A further aspect of the invention is the use of a medicament preparation which comprises as active substance the yellow fever vaccine strain 17D for intranasal vaccination against yellow fever. A live, attenuated 17D vaccine strain is preferably used. It has been found, surprisingly, that on administration of the active substance through the nose it is possible to achieve a reliable immune response leading to the expectation of reliable vaccine protection.

The invention further comprises the use of an active substance comprising the yellow fever vaccine strain 17D for producing a medicament for intranasal vaccination against yellow fever.

Claim 1 of 2 Claims

What is claimed is:

1. A method for inducing protective immunity against yellow fever virus in a human subject, comprising administering intranasally a live, attenuated yellow fever virus to a human subject wherein the live, attenuated yellow fever virus is administered to the subject in an amount effective for inducing a binding and a neutralizing antibody response.

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