2770. Intrapulmonary Vaccination with an M Protein-Deficient Respiratory Syncytial Virus (RSV) Vaccine Protects Infant Baboons Against an RSV Challenge

BACKGROUND: RSV infection is a major cause of lung disease in infants, yet there is no licensed vaccine. We are developing a live RSV vaccine with a deletion of the M protein (“Mnull RSV”). The RSV M protein is responsible for assembling newly synthesized RSV proteins into intact virus. Mnull RSV infects cells, replicates all proteins except M, and incites antibody and T-cell responses but, in the absence of the M protein, cannot replicate and infect other cells. We wished to show that vaccination with Mnull RSV directly into the lung in early infancy induces persistent neutralizing antibody (NA) responses that protect infant baboons against an RSV challenge. METHODS: Two-week-old infants were vaccinated with a single dose of Mnull RSV (8 × 10(7) vaccine units) or a sham preparation instilled into an endotracheal tube. Infants were observed continuously for signs of rapid breathing using infrared cameras. Four to six months later, serum RSV NA titers were determined, and infants were challenged intratracheally with the human RSV A2 strain. Respiratory rates were calculated daily. On days 0, 5, 7, and 12 after infection, arterial blood was drawn for blood gas analysis, lung function was assessed using a pneumotachometer, and bronchoalveolar lavage was performed for virus titrations. RESULTS: At 4–6 months following vaccination, RSV NA was present at a mean titer of 192 in sera of Mull RSV recipients, but was undetectable in sera of sham vaccinated animals. Animals were then challenged with RSV, and sham vaccinated animals developed increased respiratory rates, increased alveolar-arterial (A-a) oxygen gradients, and BAL viral titers on day 5 were 3,500 pfu/mL. In contrast, Mnull RSV vaccinated animals had lower respiratory ratios throughout the length of the study (P = 0.038), lesser A-a gradients (improved oxygenation) vs. controls, and no virus was recovered from BAL fluids (P < 0.0001). CONCLUSION: Intrapulmonary vaccination of infantswith Mnull RSV at 2 weeks of age results in strong RSV NA responses that persist beyond the length of an average RSV season. Mnull RSV recipients were protected against tachypnea, reduced oxygenation and viral replication for at least 4–6 months following vaccination. We will next study intrapulmonary vaccination administering Mnull RSV via a nebulizer. DISCLOSURES: All authors: No reported disclosures.