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Bronchiolitis is a lower respiratory tract disease, which can affect children under two years of age and young bovines. In animals, the Respiratory Syncytial Virus (RSV) affects 70 % of the herds despite vaccination campaigns. Morbidity and mortality (2-3 % to 20% in some breeding farms) cause an important economic burden. In humans, bronchiolitis is an epidemic winter disease and there is currently no vaccine available. 500,000 babies are infected every year in France and bronchiolitis is a common cause of hospitalization (2 -5% of ill children). Severe bronchiolitis is moreover a major risk factor for asthma in later infancy.

The bovine and human RSVs, which are responsible for 70 % of human and bovine bronchiolitis, are distinct but very closely related. There is 94% sequence identity between human and bovine viral nucleocapsid proteins, a piece of the protective shell of the viral genome. Thus, a vaccine using this protein could be effective in both humans and animals. This protein, named protein N, is one of the most abundant proteins in viral particles. However because of strong self-agglutination, this protein was very difficult to purify and to obtain in large amounts. Protein N has not often been used in vaccine development, despite being very antigenic (able to trigger an effective immune response). In developing a new production process with genetic tools (INRA patent), researchers have resolved the problem of protein N availability. Synthesized by bacteria, protein N was purified in homogenous rings of 10 – 11 protein subunits (10 nm diameter), named N SRS for N Sub-nucleocapsid Ring Structure.

After inoculation by the nasal route, these nanoparticles protected mice against human RSV. After two successive administrations of nanoparticles, RSV replication in the lungs was markedly decreased. The researchers showed that parenteral immunization was less effective, suggesting that an interaction between N SRS and mucosal immune cells of the respiratory tract is necessary to trigger an effective immune protection against viral infection.

The vaccine formulation may be further optimized. The adjuvants, chemical substances that modulate immunogenicity of a vaccine, remain to be determined to obtain a long lasting protection against bronchiolitis. Very immunogenic upon nasal administration, N SRS nanoparticles are a promising vaccine candidate against RSV to prevent human and animal respiratory disease.

For further information:

• Sub-nucleocapsid Nanoparticles : A nasal vaccine against Respiratory Syncytial Virus. ROUX X., DUBUQUOY C., DURAND G., TRAN-TOLLA T., CASTAGNE N., BERNARD J., PETIT-CAMURDAN A., ELEOUET J.F., RIFFAULT S. PLoS One. 2008 Mar 12;3(3):e1766.
• The nine C-terminal amino acids of the respiratory syncytial virus protein P are necessary and sufficient for binding to ribonucleoprotein complexes in which six ribonucleotides are contacted per N protein protomer. TRAN TL, CASTAGNE N, BHELLA D, VARELA PF, BERNARD J, CHILMONCZYK S, BERKENKAMP S, BENHAMO V, GRZNAROVA K, GROSCLAUDE J, NESPOULOS C, REY FA, ELEOUËT JF. J Gen Virol. 2007 Jan;88(Pt 1):196-206.

• Patent WO/2006/117456 : PREPARATION DE COMPLEXES SOLUBLES PROTEINE N-PROTEINE P TRONQUEE OU DE PROTEINE N SOLUBLE D'UN VIRUS DE LA FAMILLE DES PARAMYXOVIRIDAE ET LEURS UTILISATIONS VACCINALES
• Patent WO/2007/119011: PROTEINES DE FUSION PROTEINE N D'UN VIRUS DE LA FAMILLE DES PARAMYXOVIRIDAE-PROTEINE D'INTERET