1229. Development of an Infant Baboon Model of Respiratory Syncytial Virus Infection
Session: Poster Abstract Session: RSV and Other Viral Respiratory Infections in Children
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • Papin_RSV_IDSA_2011du.png (578.8 kB)
  • Background: 

    Respiratory syncytial virus (RSV) is a major respiratory pathogen of infancy. RSV infection annually results in more than 120,000 hospitalizations in the USA, and more than 300,000 deaths worldwide. There is no approved vaccine, and no effective specific form of therapy. This gap is largely due to the absence of a useful animal model in which to study vaccines, antivirals and immune modulating agents.

    Methods: 

    We infected 4 week infant baboons with 2-4 x 108 units of RSV either intranasally (IN) or intratracheally (IT) with a human A2 strain of RSV. Respiratory rate, heart rate, rectal temperature, oxygen saturation (O2sat), and oral formula intake were determined at baseline and over the next 14 days after infection. Bronchoalveolar lavage (BAL) was performed at baseline and at intervals following infection in order to determine the number and types of inflammatory cells present, and the titer of RSV in BAL fluids. Selected animals were sacrificed on Day 8 after infection for study of lung pathology. Uninfected baboons were treated according to the same protocol.

    Results: All baboons infected intracheally, and 50% of those infected IN, developed tachypnea (>80 breaths per minute), hypoxia (O2sat = 93-94%), and reduced feeding (< 50% of pre-infection volume) from Day 3-8 after infection, but hypoxia persisted up to Day 10. No animals died. Control animals did not develop tachypnea, hypoxia or reduced feeding. Macrophages and neutrophils were the predominant cell types seen in BAL fluids following infection. Lymphocytes were no more frequent in BAL fluids from infected baboons than in those of controls. Pathologic analysis of lung tissue revealed interstitial pneumonia with hypertrophy of bronchiolar epithelium in infected baboons.

    Conclusion: Similar to human infants, infant baboons infected with human RSV develop tachypnea, hypoxia and reduced feeding persisting for one week after infection. The nature of the cellular inflammatory response is also similar to that of human infants, and unlike that of other animal models. The infant baboon represents an excellent model for the study of the pathogenesis of RSV infection, as well as for determining the safety and efficacy of vaccines, antivirals and immunomodulating agents.


    Subject Category: P. Pediatric and perinatal infections

    James Papin, PhD, Veterinary Medicine, Oklahoma University Health Science Center, Oklahoma City, OK, Roman Wolf, DVM, Veterinary Medicine, Oklahoma University Health Sciences Center, Oklahoma City, OK, Gary White, MMS, DVM, Oklahoma University Health Science Center, Oklahoma City, OK, Sara Moore, BS, Pediatrics, Oklahoma University Health Science Center, Oklahoma City, OK and Robert Welliver Sr., MD, Pediatrics, Oklahoma University Health Sciences Center, Oklahoma City, OK

    Disclosures:

    J. Papin, None

    R. Wolf, None

    G. White, None

    S. Moore, None

    R. Welliver Sr., None

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.