Respiratory syncytial virus (RSV), the major cause of lower respiratory tract disease in infants, is thought to infect the upper airways before spreading to the lower respiratory tract. A rhesus monkey model of RSV infection after upper airway inoculation was used to test the protective effect of intranasal treatment with HNK20, a mouse monoclonal IgA antibody against RSV F glycoprotein. HNK20 was administered once daily for 2 days before RSV challenge and 4 days after challenge. Treatment with 0.5 mg/kg HNK20 reduced viral shedding in the nose, throat, and lungs by 3-4 log10/mL (P < or = .002). All monkeys developed RSV neutralizing antibody in serum, even in the absence of detectable viral replication. Neutralizing concentrations of monoclonal antibody remained in nasal secretions for > 1 day after treatment. These results suggest that nose-drop application of monoclonal antibody could provide convenient and effective protection against RSV infection in human infants at risk of severe lower respiratory tract disease.

Virologic and immunologic effects of immunomodulation during primary simian immunodeficiency virus (SIV) infection were examined in monkeys treated with cyclosporin or vehicle for 32 days beginning 5 days before SIV inoculation. Duration of antigenemia decreased in 5 of 7 treated monkeys, 2 having delayed onset and peak of antigenemia. Although proviral DNA levels in blood and lymph nodes and infected cell numbers in lymph nodes were transiently decreased, levels were similar to those in controls by day 14. The CD4:CD8 ratio and percentage of CD4+ CD29+ cells decreased in controls 14 days after inoculation, but this decrease was delayed in treated monkeys. Two treated monkeys demonstrated rapid disease, with progressive antigenemia preceding early deaths 90-96 days after inoculation. Nevertheless, immunomodulation influenced the kinetics of primary SIV infection in some monkeys, supporting the rationale of careful exploration of the strategy of interference with the heightened state of cellular activation together with direct antiretroviral therapy in human immunodeficiency virus infection.

In this study, 11 SMM were grouped and inoculated with differing doses of SMM-origin My cobacterium /eprae (ML) between 4•5 x 10 8 and I x 10 9 by either combined IV IIC routes or by IV or IC route alone. The combined route was the most effective in eliciting progressive, disseminated LL leprosy. In all, 6 of 7 SMM inoculated by the combined routes developed leprosy requiring treatment at some point. Only 1 of 4 inoculated by a single route developed persisting leprosy requiring chemotherapy. Either no disease or spontaneous regression of initial disease occurred in the other 3 animals inoculated by a single route. Doses in excess of I x 10 9 ML were more effective than lesser doses. An association was observed between the development of IgG anti-PGL-I ELISA OD values and resistance to leprosy and between IgM anti-PGL-I and leprosy progression or susceptibility. Serum PGL-I antigen levels, determined by dot ELISA, paralleled disease severity longitudinally. High positive OD values of anti-LAM IgG prior to ML inoculation were observed in the majority ofleprosy susceptible SMM in contrast to negative levels in more resistant animals. Anti LAM IgG OD values exceeded the positive cutoff point after inoculation in 5 of II SMM; 3 of these 5 had concurrent detectable serum levels of PGL-I antigen. We previously observed that longitudinal serologic data from sooty mangabey monkeys (SMM) (Cercocebus torq uatus aty s) experimentally inoculated with My cobacterium /eprae (ML) may provide indicators for susceptibility to leprosy. l , 2 In that study,

Seven of eight rhesus monkeys (RM) coinfected with simian immuno deficiency virus (SIV) and My cobacterium leprae harboured acid-fast bacilli (AFB) at sites of dermal inoculation and/or at disseminated sites at times of humane sacrifice (up to 270 days post-M. leprae inoculation) due to SIV-induced debilitation or, in one long term survivor's case, to date over 3 years post-M. leprae inoculation. Detectable AFB were cleared in biopsies of inoculation sites of RM inoculated with M. leprae alone after 63 days postinoculation; these sites have, so far, remained AFB-negative, thereafter. Compared to animals infected with M. leprae alone, RM coinfected with SIV plus M. leprae showed: 1, completely suppressed serum antibody responses to M. leprae specific PGL-I antigen, but strong anti-SIV Gp 120 antibody responses; 2, impaired sensitization of blood mononuclear cells (MNC) to in vitro recognition of M. leprae specific antigens in blastogenic stimulation assays; 3, impaired in vitro responses of blood MNC to nonspecific (ConA) blastogenic stimuli; and 4, early post-M. leprae inoculation, there was a significant incremental diminution of percentages of blood CD4+CD29+ T-cells in addition to the existing SIV-induced diminished percentages of CD4+CD29+ T-cells. The results indicate that humoral and cellular immune responses to M. leprae antigens are compromised in M. leprae-inoculated RM previously infected with SIV. These results provide an immunologic basis for the demonstration of enhanced M. leprae persistence or leprosy susceptibility in SIV-M. leprae coinfected RM.

Rhesus and sooty mangabey monkeys (RM and SMM) were vaccinated and boosted with BeG or BeG + low dose (LD) or high dose (HD) heat-killed My cobacterium leprae (HKML). One group was not vaccinated. Except for a group of controls, all monkeys were challenged with live M. leprae. All animals were studied longitudinally to determine antileprosy protective efficacy. BeG reduced the numbers of RM with histopathologically-diagnosed leprosy by 70% and slowed and ameliorated the appearance of symptoms. BeG + LDHKML reduced the number of RM with leprosy by 89% and BeG + HDHKML by 78%. BeG did not protect SMM from developing leprosy, but disease progress was slowed; disease in SMM was exacerbated by the addition of HKML to the vaccine. RM, as a species, are prone to paucibacilJary (PB) forms of leprosy, whereas SMM are prone to multibacilJary (MB) forms. Thus, BeG vaccination offers significant protection from clinical disease and slows/ameliorates the rate of progression/degree of disease at the PB end and appears to at least ameliorate symptoms at the MB end of the leprosy spectrum. BeG + HKML protects at the PB end and exacerbates disease progress at the MB end of the leprosy spectrum.