Intranasal yellow fever vaccination

Details Intranasal yellow fever vaccination Intranasal yellow fever vaccination

2000-06-22

2002-01-08

Stucker, Jeffrey (Department: 1648)

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

Virus or component thereof

C424S093600, C435S235100

Reexamination Certificate

active

06337073

ABSTRACT:

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 10
3
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 (D
2
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.
The invention is explained further by the following examples and by FIG.
1
.
FIG. 1
shows neopterin/creatinine levels in monkeys vaccinated intranasally, perorally and subcutaneously, depicted as multiple of the baseline level (level before vaccination). Black symbols refer to monkeys positive in the virus isolation and vaccinated intranasally or perorally (+=8488, ▪=1655, &Dgr;=1635, ↑=1637, ⋄=1863, −=1889, x=1891; the numbers in each case indicate the identification number of the experimental animal) . The white symbols refer to the four monkeys immunized subcutaneously as controls (=8482, ⋄=8493, &Dgr;=8494, ∘=8495), whose levels are shown in the lower diagram.


REFERENCES:
patent: 4500512 (1985-02-01), Barme
patent: 0 877 086 (1998-11-01), None
Gibson et al. “Effect of administration of sodium aurothiomalate on the virulence of yellow fever viruses in adult mice”, Vaccine, vol. 8, No. 6 (Dec. 1990), pp. 590-594. QR189.V82.*
“Requirements for yellow fever vaccine (Requirements for Biological Substances No. 3, revised 1995)” WHO Technical Report Series, No. 872, 1998, pp. 30-50.
Jennings et al., “Analysis of yellow fever virus isolated from a fatal case of vaccine-associated human encephalitis”, Journal of Infectious Diseases, vol. 169, No. 3, March 1994, pp. 512-518.
Barrett et al., “Comparison of neurovirulence of different strains of yellow fever virus in mice.” Journal of General Virology, vol. 67, No. 4, April 1986, pp. 631-637.
Dunster et al., “Attenuation of virulence of flaviviruses following passage in HeLA cells.”, Journal of General Virology, vol. 71, No. 3, March 1990, pp. 601-607.

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