Desired immune response characteristics in an RSV vaccine: What infants tell us
Year: 2009
Type: article
Study design: Observational Study
Abstract: Respiratory syncytial virus (RSV) represents an important target for vaccine development. The design of an \neffective vaccine for infants is hindered by a lack of knowledge of the nature of the protective immune response to \nRSV infection in this age group. To understand immune mechanisms in the infant lung, we examined respiratory \nsamples from infants 0-6 months with severe RSV LRI, and compared these to uninfected infants. At the peak of \nRSV infection (but not in controls), activated macrophages (CD14+, CD16+, CD68+) and B lymphocytes (CD20+, \nIgA+, IgM+, IgG+) are prominent while dendritic cells (MHCII+), T lymphocytes and T cell associated cytokines \n(Welliver et al, 2007 J. Infect. Dis. 195:1126) are not. In nasopharyngeal secretions, polyreactive IgG, IgM and \nIgA recognizing RSV virions and apoptotic debris were readily detected. The presence of polyspecific local \nantibodies strongly correlated with mucosal expression of BAFF, a T-independent, B-cell activating cytokine, which \nlocalized in lung tissue to RSV-infected and apoptotic respiratory epithelium. Polyspecific local antibodies were \nassociated with better oxygenation at presentation. In vitro, products of RSV infected epithelium, such as BAFF, \nTLR7 ligand, and type I IFN synergistically elicited Ig and cytokine production from cultured B lymphocytes, while \nvirions alone had no such effect. Our data suggest that in infants, innate immune factors released from RSV \ninfected epithelium elicit T independent, polyspecific B cell responses which have modest protective effects. \nPerhaps the lack of antigen presentation via dendritic cells in infant respiratory tissue impedes the development of \nT-dependent responses and contributes to severe disease susceptibility in this age group. RSV vaccine strategies \ntailored for infants should recruit and mature lung-associated macrophages and dendritic cells, in order to deliver \nantigen to elicit long-lasting, T-cell dependent immunity. Alternatively, an RSV vaccine that promotes local innate \nB lymphocyte responses might elicit short-term protection, bridging the gap between maternal antibody protection \nand the development of mature immune responses found in older children.
Source: Procedia in Vaccinology
Authors: Jennifer L. Reed, Luis Avendaño, Luis Velozo, Robert C. Welliver
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W2065238629