Science

Development of the first intranasal live attenuated multivalent vaccine against viral bronchiolitis and pneumonia

RSV and HMPV

First causes of respiratory viral infections in children and older adults

RSV

Discovered in 1956

human Respiratory Syncytial Virus

HMPV

Discovered in 2001

Human MetaPneumoVirus

Two causes of Bronchiolis & Pneumonia

No licensed HMPV vaccine available

Pfizer subunit RSV vaccine licensed for older adults >60, and maternal immunisation GSK adjuvanted subunit RSV vaccine licensed for older adults >60 Sanofi RSV-MAbs licensed for new-born passive immunisation

High Burden of Disease (BoD) in children and older adults

Children

BoD of HMPV almost half of RSV

Older adults

BoD of HMPV at same level as RSV

RSV and HMPV mortality in children mainly in developing countries

(1) Williams JV, Edards KM, Weiberg GA et al. Popula;on-based evidence of human metapneumovirus infec;on among hospitalised children. J. Infect. Dis. 2010;368(7):633-643
(2) Hall et al. The Burden of Respiratory Syncy;al Virus Infec;on in Young Children. N Engl J Med. 2009 February 5; 360(6): 588–598
(3) Edwards KM, Y Zhu, M.R. Griffin, G.A. Weinberg, C.B. Hall, P.G. Szilagyi, et al. Burden of human metapneumovirus in young children. N. Engl. J. Med., 2013;368(7):633-643
(4) K. Widmer et al, Rates of Hospitaliza;ons for Respiratory Syncy;al Virus, Human Metapneumovirus, and Influenza Virus in Older Adults, JID 2012:206

METAVAC®

HMPV-based Proprietary versatile viral vaccine platform – in vivo PoC

Base: highly replicative and hyperfusogenic clinical HMPV strain C-85473 (reverse genetic)

Non-reversible and functional attenuation through deletion of the SH gene

Infectious and replicative in Human Airway Epithelium/low induction of pro-inflammatory cytokines

No pathogenicity or clinical sign in in-vivo ouse model – no enhanced disease

Efficient immune cell recruitment and low inflammatory profile in lung

Protection against HMPV challenge and strong induction of homologous/heterologous neutralizing Ab

Possibility to include other respiratory virus antigens

Cytopathic effects of HMPV at 3 days post-infection (fluorescent microscopy)

Cytopathic effects of Metavac® at three days post-infection (fluorescent microscopy)

Observation of Metavac® by transmission electron microscopy

METAVAC® RSV-HMPV bivalent intranasal vaccine candidate

Preclinical in vivo PoC – Protection against RSV and HMPV

HMPV LAV, Infectious, replicative and expressing F-HMPV and F-RSV

Low induction of pro-inflammatory cytokines in Human Airway Epithelium (HAE)

No pathogenicity or clinical sign in murine model - no enhanced disease

Protection against lethal HMPV in-vivo challenge / strong induction of homologous/heterologous NAbs against HMPV-A & B strains

Protection against RSV in-vivo challenge / strong induction of homologous/heterologous NAbs against RSV-A & B strains

Stimulation of mucosal IgA secretionand Th1 cellular response

Palivisumab anti-F RSV staining

HMPV challenge

RSV challenge mock-vaccinated

RSV challenge bivalent vaccinated

Towards an
Industrial Vaccine

METAVAC® RSV-HMPV produced on GMP-grade Vero

Fully functional in vitro (human epithelium) and in vivo preclinical models
Infectious and efficiently replicative
Ongoing Process optimistion

Genomic stability of bivalent METAVAC® RSV-HMPV

No deleterious mutation (antigenic, polymerase) after 10 passages

Shelf life

Basic formulation was validated for 6 months stability (complete preservation of infectious titer at 4°C)

Current Target
Product Profile

Target population

Immunisation of children

46,000,000

Children below 5 years (EU + US)

Immunisation of older adults

151,000,000

older adults above 65 (EU + US)

Metavac® RSV-HMPV

Target population (EU + US)

200,000,000

Expected peak sales

1,7m€