Respiratory Syncytial Virus Infections in Infants Affected by Primary Immunodeficiency

Abstract

Primary immunodeficiencies are rare inherited disorders that may lead to frequent and often severe acute respiratory infections. Respiratory syncytial virus (RSV) is one of the most frequent pathogens during early infancy and the infection is more severe in immunocompromised infants than in healthy infants, as a result of impaired T- and B-cell immune response unable to efficaciously neutralize viral replication, with subsequent increased viral shedding and potentially lethal lower respiratory tract infection. Several authors have reported a severe clinical course after RSV infections in infants and children with primary and acquired immunodeficiencies. Environmental prophylaxis is essential in order to reduce the infection during the epidemic season in hospitalized immunocompromised infants. Prophylaxis with palivizumab, a humanized monoclonal antibody against the RSV F protein, is currently recommended in high-risk infants born prematurely, with chronic lung disease or congenital heart disease. Currently however the prophylaxis is not routinely recommended in infants with primary immunodeficiency, although some authors propose the extension of prophylaxis to this high risk population.

Treatment with novel RSV Ig RI-002 controls viral replication and reduces pulmonary damage in immunocompromised Sigmodon hispidus

“…There is a well-defined segment of patients with immune deficiency diseases that require regular infusions of Ig to reconstitute their deficient humoral Ab compartment and who are also extremely susceptible to RSV disease. [43][44][45] With the withdrawal of RespiGam from the market, an important IVIG product in the arsenal for controlling RSV disease in vulnerable populations is no longer available. The improved efficacy of IVIG vs palivizumab against RSV in HSCT patients 17,19 suggested that broader spectrum Ab may be required.…”

Retinoic acid-inducible gene-I-like receptor (RLR)-mediated antiviral innate immune responses in the lower respiratory tract: Roles of TRAF3 and TRAF5

“…We showed that HPAEpiCs express lower levels of IFN-β in response to dsRNA compared with HBEpCs. This finding may indicate a lesser contribution of AECs in antiviral innate immune responses in lung because 13 of the abundance of professional immune cells in this tissue site.…”

“…Newborns and infants, particularly those born prematurely, are susceptible to severe viral infections of the lower respiratory tract (LRT) because of the small size of the airways in which airway edema and sloughing of epithelial cells cause atelectasis, subsequent mismatch of ventilation, perfusion and reduced oxygenation [13]. Once a host is exposed to a virus on the surface of the respiratory tract, the antiviral innate immune response is activated, which determines the serum antibody response that prevents progression to LRT infection via virus neutralization [13][14][15].…”

“…Once a host is exposed to a virus on the surface of the respiratory tract, the antiviral innate immune response is activated, which determines the serum antibody response that prevents progression to LRT infection via virus neutralization [13][14][15]. Epithelial cells are among the first targets of respiratory viruses and serve both as a physical barrier and as the first line of innate host defense against viruses, such as respiratory syncytial virus (RSV), influenza virus, and human metapneumovirus [16].…”

RI-002, an intravenous immunoglobulin containing high titer neutralizing antibody to RSV and other respiratory viruses for use in primary immunodeficiency disease and other immune compromised populations

“…Supplementation with immunoglobulins (IG) has been considered the standard of care for the treatment of patients with a variety of antibody production disorders due to B cell or B and T cell abnormalities, collectively referred to as primary immunodeficiency diseases (PIDDs) [1]. While regular infusions with IG prevent the vast majority of serious bacterial infections within this population, there is no single prophylactic regimen that provides protection against the wide range of viral pathogens to which these patients are susceptible [2][3][4][5][6][7][8]. In the USA, there are several commercially available IG products that meet minimum standards of concentrations of antibodies to diphtheria toxoid (≥1.21 U/mL), measles (≥0.60 CBER reference), and polio (≥0.28 CBER reference) viruses in conformance with the US FDA guidance 21CFR 640 subpart J [9].…”