Natural Reinfection with Respiratory Syncytial Virus Does Not Boost Virus-Specific T-Cell Immunity

Abstract

To determine the role of respiratory syncytial virus (RSV)-specific cell-mediated immunity during natural reinfection, we investigated whether RSV-specific T-cell responses protect against reinfection and, subsequently, whether reinfection boosts virusspecific memory. In a cohort of 55 infants who were hospitalized for RSV bronchiolitis, RSV-specific lymphoproliferative responses in the peripheral blood were measured at three time-points: on admission, 4 wk after admission, and 1 y later, after the second winter season. Memory was defined as a stimulation index (SI) Ͼ2. During the second winter season, nasal secretions were collected in every case of a runny nose. Reinfection was diagnosed if immunofluorescence or PCR was positive for RSV. Virus-specific memory was found in one child on admission for primary RSV infection, whereas 4 wk later 44 infants (80%) had memory. Reinfection with RSV was found in 23 infants (43%) during the second winter season. After the second season, memory was found in 20 infants (38%). No differences in SI after the second winter season were found between infants with and without reinfection (2.3 versus 2.1). However, a highly significant correlation was found between SI measured 4 wk after primary RSV infection and SI after the second winter season (r ϭ 0.40, p ϭ 0.001). In conclusion, RSV-specific T-cell responses did not provide protection against reinfection. Moreover, reinfection did not boost RSV-specific T-cell proliferation. To explain both findings, it is hypothesized that RSV-specific T cells fail to expand in vivo upon reinfection. RSV is one of the most important respiratory pathogens in infancy causing the majority of lower respiratory tract infections during the winter season. Hospitalization rates for RSV illness are 1-30 cases per 1000 infants Ͻ1 y of age (1-3). In hospitalized infants with RSV bronchiolitis, mechanical ventilation is required in 7-21% of cases (4 -6). Mortality in RSV-infected infants with lower respiratory tract symptoms is Ͻ1% (7).Reinfection with RSV occurs frequently and usually has a mild character with symptoms of uncomplicated upper respiratory tract infection (8). Neutralizing antibodies induced by primary RSV infection appear to provide only partial protection for a limited period of time, which does probably not last until the subsequent RSV season (8,9). Evidence that intact cell-mediated responses play a role in clearance of the virus and protection against reinfection was derived from animal studies (10). In humans, little information is available on the role of virus-specific CMI induced during primary infection in the protection against reinfection with RSV.Currently, no vaccine for RSV is available. In the 1960s, a formalin-inactivated vaccine was used in infants (11). No protection against naturally acquired RSV was observed. In contrast, enhanced disease and increased mortality were observed during RSV infection after vaccination. CMI has been implicated in the pathogenesis of this phenomenon (12

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Evolution of Human Respiratory Syncytial Virus (RSV) over Multiple Seasons in New South Wales, Australia

“…This is thought to reflect strong immune pressure and the subsequent 66 generation of escape variants, in a process analogous to antigenic drift in the hemagglutinin (HA) 67 protein in influenza A virus [12,13]. Hence, reinfection with RSV is commonplace [14,15] …”

T Helper Lymphocyte Response to Respiratory Syncytial Virus and Its Components in Patients with Respiratory Allergy and Nonatopic Controls

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