Respiratory syncytial virus (RSV) vaccine candidate
MVA-BN RSV is designed to induce a balanced antibody and T-cell response which we believe delivers the desired immune response. Because our MVA-BN RSV vaccine expresses the two main RSV surface proteins (F and G), it encourages cross-strain reactivity and provides protection against both RSV subtypes (A and B). In addition, our MVA-BN RSV vaccine contains conserved internal proteins, which we believe enable the vaccine to achieve broader T-cell response than would be possible without them.
MVA-BN RSV, has been shown to be highly efficacious in preclinical models, demonstrating both an antibody and a T-cell response from the immune system. Published data have shown that both responses are required to prevent an RSV infection. In addition to antibodies in the blood, the presence of antibodies in the mucous membranes is an important barrier to infection by RSV. Preclinical studies have shown that MVA-BN RSV brings about such an antibody response in the mucosa.
Results from a randomized, placebo-controlled Phase 1 trial in 63 healthy adults, ages 18-65, were reported in May 2016. Subjects were enrolled into three groups to receive two different dose levels of MVA-BN RSV: Low Dose/Adult, High Dose/Adult and High Dose/Elderly. The Elderly group enrolled subjects of 50-65 years of age in order to evaluate the immune responses in a population that is one of the key targets for the vaccine.
MVA-BN RSV was well tolerated, with no unexpected or serious adverse reactions. The vast majority of events represent local and systemic reactions typical for vaccines. A significant boost in antibodies and T cells against RSV was measured in all groups following vaccination with MVA-BN RSV including:
- Neutralizing antibodies against both RSV subtypes A & B.
- In elderly subjects, there was a significant increase in both blood IgG and IgA antibodies, the latter a specialized antibody that is transported from blood to mucosal surfaces (e.g. nose, throat, lungs).
- T cell responses against RSV were significantly boosted in elderly subjects vaccinated, with a 3-5 fold increase observed against RSV or the 3 RSV proteins tested to date, including the RSV surface proteins F (fusion) and G (glycoprotein) and the highly conserved nucleocapsid protein (N).
- The broad T cell response stimulated in the majority of elderly subjects is cross reactive against both RSV subtypes.
A Phase 2 study in elderly was initiated in October 2016. Top-line results from the study are anticipated around mid-2017 and will provide important information for a subsequent Phase 2b field efficacy study, which is planned for initiation later in 2017.