Inactivation of respiratory syncytial virus by generic hand dishwashing detergents and antibacterial hand soaps.

In an in-vitro test, generic liquid hand dishwashing detergents were as much as 100-fold more effective than proprietary antibacterial soaps in inactivating respiratory syncytial virus (RSV). The use of such detergents for hand washing during annual RSV epidemics, or the incorporation of their antiviral components into antibacterial soaps might be considered to limit nosocomial spread.

Immunoprophylaxis of group B respiratory syncytial virus infection in cotton rats.

Two antigenic groups of respiratory syncytial virus (RSV) have been identified: A (RSV/A) and B (RSV/B). Topical administration of human IgG screened for high titers of antibody to RSV/A (RSVIg) is protective against RSV/A infection in the cotton rat model. The study attempted to determine if topical RSVIg would also be protective against RSV/B. Cotton rats were pretreated intranasally with RSVIg or with monospecific antiserum obtained from animals previously infected with RSV/A or RSV/B (day 0), challenged intranasally with RSV/A or RSV/B (day 1), and sacrificed for virus titration (day 5). Cotton rat antiserum to RSV/B protected against RSV/A and RSV/B, while antiserum to RSV/A protected only against RSV/A. RSVIg, although prepared on the basis of activity against RSV/A, was also protective against RSV/B.

Unilateral nasal infection of cotton rats with respiratory syncytial virus allows assessment of local and systemic immunity.

An in vivo model for the study of local and systemic effectors of immunity to respiratory syncytial virus (RSV) is described. Cotton rats (Sigmodon fulviventer) inoculated in one nostril with a small volume (2 microliters) of virus suspension contracted a unilateral nasal infection which did not extend to the contralateral nasal turbinates, nor to the lungs. Immunity to subsequent RSV challenge could be induced by small priming doses ( < 10 p.f.u. per animal), but was dependent upon viral replication, as virus inactivated by UV light was not immunogenic. Immunity occurred in the absence of detectable neutralizing serum antibody. The onset of resistance to viral challenge occurred simultaneously in ipsilateral nasal, contralateral nasal and pulmonary tissues. However, low levels of transient viral replication occurred in contralateral nasal turbinates and in lungs following virus challenge, thus indicating that local components of immunity acting at the ipsilateral site of infection were more effective than systemic components acting at the other sites. Further evidence is provided to suggest that three types of immunological effectors - local, persistent, systemic and transient systemic - participate in the immune response to RSV infection.

Topical immunoglobulin is an effective therapy for parainfluenza type 3 in a cotton rat model.

A cotton rat model was used to test the efficacy of topical immunotherapy against parainfluenza type 3 (PIV3) infection. On day 3 after experimental infection with 10(5.5) pfu of PIV3, animals were treated with 2-fold dilutions of convalescent cotton rat serum or with one of two purified human immunoglobulin preparations; all three had moderate titers of anti-PIV3 neutralizing antibody (range, 1:200-1:1000). Therapy with high concentrations of all three preparations resulted in significant reductions of > or = 2 logs (> or = 100-fold) of pulmonary virus titers compared with titers for control animals. Little or no reduction in virus titers were seen in nasal tissues.

A cotton rat model of effectors of immunity to respiratory syncytial virus other than serum antibody.

A model for studying effectors of immunity to respiratory syncytial virus (RSV) was developed. Paris of inbred cotton rats (Sigmodon hispidus) were joined surgically using the technique of parabiosis. One week later, one animal of each pair was primed intranasally with a small volume of RSV suspension. Fourteen days after priming, both animals of each pair were bled for determination of serum neutralizing antibody titers, and challenged intranasally with a standard dose of RSV suspension. Single, unprimed cotton rats were challenged concomitantly and served as controls. Four days after challenge, all animals were sacrificed for virus titration of nasal tissues and lungs. Parabiosed cotton rats were surgically separated at varying intervals between priming and challenge (days 7, 9, 12, or 14 after priming) or were kept joined until sacrificed (day 18). Significant transfer of nasal and pulmonary immunity from primed to unprimed parabionts began 9 days after priming, gradually increasing through 18 days. Resistance to RSV challenge in spite of low levels of serum neutralizing antibody suggests that non-antibody immunologic mediators were responsible for the transferred immunity. Evidence is presented for three broad categories of RSV immunologic effectors: systemic, local with a transient systemic phase, and local without a systemic phase. These categories are now amenable to further study using the described model.

Systemic immunoprophylaxis of nasal respiratory syncytial virus infection in cotton rats.

The cotton rat model was used to test whether systemically administered immunoglobulin could protect nasal tissues against low challenge doses of respiratory syncytial virus (RSV). Animals were pretreated by intraperitoneal injection of human immunoglobulin with moderate (1:2226) or high (1:15,000) neutralizing antibody titers to RSV (day 0), challenged intranasally with RSV Long at doses ranging from 10(1) to 10(5) pfu (day 1), and sacrificed for virus titration (day 5). Pretreatment with moderate-titer immunoglobulin effected complete or near complete nasal protection against low to moderate (10(1)-10(3) pfu) RSV challenge doses and a significant reduction in nasal RSV titers at high (10(4)-10(5) pfu) challenge doses. Pretreatment with high-titer immunoglobulin effected near complete nasal protection at an RSV challenge dose of 10(3) pfu and highly significant and significant reductions in nasal RSV titers at challenge doses of 10(4) and 10(5) pfu, respectively. Immunoprophylaxis effected complete or near complete pulmonary protection at all RSV challenge doses.

Bovine respiratory syncytial virus protects cotton rats against human respiratory syncytial virus infection.

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory infections in infancy. No vaccine against this virus has yet been protective, and antiviral drugs have been of limited utility. Using the cotton rat model of HRSV infection, we examined bovine respiratory syncytial virus (BRSV), a cause of acute respiratory disease in young cattle, as a possible vaccine candidate to protect children against HRSV infection. Cotton rats were primed intranasally with graded doses of BRSV/375 or HRSV/Long or were left unprimed. Three weeks later, they were challenged intranasally with either BRSV/375, HRSV/Long (subgroup A), or HRSV/18537 (subgroup B). At intervals postchallenge, animals were sacrificed for virus titration and histologic evaluation. Serum neutralizing antibody titers were determined at the time of viral challenge. BRSV/375 replicated to low titers in nasal tissues and lungs. Priming with 10(5) PFU of BRSV/375 effected a 500- to 1,000-fold reduction in peak nasal HRSV titer and a greater than 1,000-fold reduction in peak pulmonary HRSV titer upon challenge with HRSV/Long or HRSV/18537. In contrast to priming with HRSV, priming with BRSV did not induce substantial levels of neutralizing antibody against HRSV and was associated with a delayed onset of clearance of HRSV upon challenge. Priming with BRSV/375 caused mild nasal and pulmonary pathology and did not cause exacerbation of disease upon challenge with HRSV/Long. Our findings suggest that BRSV may be a potential vaccine against HRSV and a useful tool for studying the mechanisms of immunity to HRSV.

Immunotherapy of respiratory syncytial virus infection in cotton rats (Sigmodon fulviventer) using IgG in a small-particle aerosol.

To determine whether aerosolized IgG can be used effectively in the treatment of respiratory syncytial virus (RSV) infections, cotton rats were infected intranasally with RSV and treated 3 days later with human IgG containing anti-RSV antibodies delivered in a small-particle aerosol. Pulmonary histology and virus titers were determined 24 h after IgG treatment. A single 15-min exposure to aerosolized IgG did not exacerbate pulmonary pathology and effected a 50-fold reduction in pulmonary virus titer (2.95 vs. 4.67 log10 geometric mean pfu/g for untreated controls, P < .001), which was comparable to that effected by intranasally instilled IgG (50 mg/kg) (3.24 vs. 4.67 log10 geometric mean pfu/g for controls, P < .001). A 15-min exposure to aerosolized ribavirin (20 mg/mL) was not effective in reducing pulmonary virus. This study suggests that aerosolized IgG could be useful in the treatment of RSV lower respiratory tract infections and that it compares favorably with ribavirin.