Rotavirus shedding in premature infants following first immunization.

OBJECTIVE: There is limited data regarding rotavirus vaccine shedding in premature infants. We describe the natural history of rotavirus shedding in premature infants in the 2-week period following first immunization with RotaTeq(®), the pentavalent rotavirus vaccine (RV5), and the risk for symptomatic transmission to household contacts (HHC). PATIENTS AND METHODS: A prospective pilot study of 15 premature infants of gestational ages 26-34 weeks immunized with RV5 between 6 and 14 weeks chronological age on discharge from the NICU was conducted. Stool samples collected in the following 2 weeks and analyzed for rotavirus antigen by enzyme immunoassay (EIA), cell culture, and RT-PCR. Solicited adverse events were collected on study subjects and any symptoms of fever, vomiting and diarrhea in HHC. RESULTS: Rotavirus antigen shedding after immunization was detected, with positive rotavirus EIA results in 53.3% of premature infants and in 22.1% of 86 stool samples collected. Shedding rates by RT-PCR were higher with 86.7% of infants and 76.7% of samples being positive. Only 42% of EIA positive samples were positive by cell culture (8/86 total samples, 9.3%). None of 53 HHC reported symptoms of rotavirus infection during the 4 weeks following immunization of the infants. CONCLUSIONS: The findings of this study demonstrate that premature infants have positive stools by EIA, viral culture, and RT-PCR at varying time points during 2 weeks following first-dose immunization with RV5. RT-PCR shedding rates need to be clinically evaluated in the context of virus quantification by cell culture, which was low. No symptomatic transmission to HHC was detected in this study, supporting low transmissibility of vaccine virus shed by these infants born prematurely.

Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax.

Inhalational anthrax, a zoonotic disease caused by the inhalation of Bacillus anthracis spores, has a ∼50% fatality rate even when treated with antibiotics. Pathogenesis is dependent on the activity of two toxic noncovalent complexes: edema toxin (EdTx) and lethal toxin (LeTx). Protective antigen (PA), an essential component of both complexes, binds with high affinity to the major receptor mediating the lethality of anthrax toxin in vivo, capillary morphogenesis protein 2 (CMG2). Certain antibodies against PA have been shown to protect against anthrax in vivo. As an alternative to anti-PA antibodies, we produced a fusion of the extracellular domain of human CMG2 and human IgG Fc, using both transient and stable tobacco plant expression systems. Optimized expression led to the CMG2-Fc fusion protein being produced at high levels: 730 mg/kg fresh leaf weight in Nicotiana benthamiana and 65 mg/kg in N. tabacum. CMG2-Fc, purified from tobacco plants, fully protected rabbits against a lethal challenge with B. anthracis spores at a dose of 2 mg/kg body weight administered at the time of challenge. Treatment with CMG2-Fc did not interfere with the development of the animals' own immunity to anthrax, as treated animals that survived an initial challenge also survived a rechallenge 30 days later. The glycosylation of the Fc (or lack thereof) had no significant effect on the protective potency of CMG2-Fc in rabbits or on its serum half-life, which was about 5 days. Significantly, CMG2-Fc effectively neutralized, in vitro, LeTx-containing mutant forms of PA that were not neutralized by anti-PA monoclonal antibodies.