Intravenous immunoglobulin treatment of respiratory syncytial virus infections in infants and young children

Abstract

Respiratory syncytial virus (RSV)-infected cotton rats (Sigmadon hispidus) and owl monkeys (Aotus trivirgatus) showed significant reductions in RSV shedding from their respiratory tracts following parenteral therapy with human intravenous immunoglobulin (IVIG) containing high titers of RSV-neutralizing antibody. Because this therapy was well tolerated and appeared safe, a double-blind, placebo-controlled IVIG immunotherapy pilot study was performed on 35 hospitalized, RSV-infected infants and children. The treatment was well tolerated and resulted in significant reductions in nasal RSV shedding and in improvements in transcutaneous oximetry readings. However, the mean duration of hospitalization was not reduced by IVIG treatment. Followup to date has revealed no harmful effects resulting from immunotherapy of RSV infections. These studies appear to refute the hypothesis that passively acquired antibody may exacerbate RSV bronchiolitis or pneumonia in infants. Studies with larger numbers of seriously ill children will be required to determine if immunoglobulin G immunotherapy of RSV infections in infants is of clinical value.Respiratory syncytial virus (RSV) is an important respiratory pathogen of infants and young children. The virus produces annual epidemics of bronchiolitis and pneumonia in children throughout the world and causes numerous hospital admissions, substantial morbidity, and some mortality (2,5,7,15,17,30,31). Efforts to produce an effective vaccine for prevention of these infections have thus far been unsuccessful (16,19,35). Only recently, with the introduction of ribavirin, has treatment other than supportive therapy been available for children with serious RSV infections (1,6,11,12,29,32).The current studies were prompted by a series of observations: (i) pups of RSV-immune cotton rat mothers were protected from RSV infection, presumably by transplacental antibody (25); (ii) injection of serum from RSV-immune cotton rats protected nonimmune cotton rats from RSV infection (26); (iii) high-titered RSV-immune human serum and human immunoglobulin prepared for intravenous administration (IVIG) were effective for both prophylaxis and therapy of RSV infections in cotton rats and owl monkeys (13, 24); (iv) some lots of human IVIG contained substantial titers of neutralizing antibody to RSV (14); and (v) careful pathological studies of the lungs of RSV-infected animals treated with IVIG revealed no evident microscopic pulmonary abnormalities characteristic of the formation of antigenantibody complexes or other untoward pulmonary reactions (13,24). The current study was designed to determine if IVIG containing substantial levels of RSV-neutralizing antibody could be safely administered and if it would hasten clinical recovery when infused into RSV-infected, hospitalized children.

Genomewide Association Analysis of Respiratory Syncytial Virus Infection in Mice

“…To identify transcripts that may be related to the difference in phenotype with the induction of infection, the transcripts that differed between C57BL/6J and AKR/J mouse lungs at any time point (6,12,24,48,96, or 192 h) were identified using a statistical threshold of an FDR of Ͻ0.05 (equivalent to an error probability of ϳ0.01), a Ն3.5-fold difference, and an average intensity of Ն80 fluorescence units. These criteria yielded a total of 1,389 elements consisting of 1,350 unique transcripts (i.e., 39 elements were duplicates or triplicates) and included 1,121 annotated genes, 190 nonannotated RIKEN cDNAs (DNA sequences deposited in the RIKEN Bioresource Center Data Bank), and 39 unnamed or pseudogenes.…”

Binding of neutralizing monoclonal antibodies to regions of the fusion protein of respiratory syncytial virus expressed in Escherichia coli

“…In animal models, passively administered monoclonal antibodies (MAbs) to the fusion (F) glycoprotein of the virus have been found protective and, among these, those capable of neutralizing and inhibiting the fusion function of the virus in vitro are most effective . In human infants, immune globulin with high virus neutralizing activity administered intravenously has been found to be of therapeutic value (Hemming et al, 1987).…”

Respiratory syncytial virus upper respiratory tract illnesses in adult blood and marrow transplant recipients: combination therapy with aerosolized ribavirin and intravenous immunoglobulin

“…Ribavirin was combined with IVIG because studies in vitro, in animal models, and in children had suggested that immunoglobulin may be of benefit for RSV infections prophylactically as well as therapeutically. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] In addition, the University of Texas MD Anderson Cancer Center (MDACC) experience with combination aerosolized ribavirin and IVIG for the therapy of RSV pneumonia in adult BMT recipients and adults with leukemia had been favorable. 6,8 Bone Marrow Transplantation…”