Impact of Influenza on Pneumococcal Vaccine Effectiveness during Streptococcus pneumoniae Infection in Aged Murine Lung

Abstract

Changes in innate and adaptive immune responses caused by viral imprinting can have a significant direct or indirect influence on secondary infections and vaccine responses. The purpose of our current study was to investigate the role of immune imprinting by influenza on pneumococcal vaccine effectiveness during Streptococcus pneumoniae infection in the aged murine lung. Aged adult (18 months) mice were vaccinated with the pneumococcal polyvalent vaccine Pneumovax (5 mg/mouse). Fourteen days post vaccination, mice were instilled with PBS or influenza A/PR8/34 virus (3.5 × 102 PFU). Control and influenza-infected mice were instilled with PBS or S. pneumoniae (1 × 103 CFU, ATCC 6303) on day 7 of infection and antibacterial immune responses were assessed in the lung. Our results illustrate that, in response to a primary influenza infection, there was diminished bacterial clearance and heightened production of pro-inflammatory cytokines, such as IL6 and IL1β. Vaccination with Pneumovax decreased pro-inflammatory cytokine production by modulating NFҡB expression; however, these responses were significantly diminished after influenza infection. Taken together, the data in our current study illustrate that immune imprinting by influenza diminishes pneumococcal vaccine efficacy and, thereby, may contribute to increased susceptibility of older persons to a secondary infection with S. pneumoniae.

Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies

“…It is desirable if a response to a shared epitope results in virus neutralization, but it can be detrimental if a response to a non-protective epitope is dominant. In aged mice, immune imprinting of influenza virus reduced the efficacy of the vaccine against Streptococcus pneumoniae 151 . Wang et al developed a method that measures the antigenic distance between different strains to predict the immune response to a particular strain 152 .…”

Human monoclonal antibodies protect against viral-mediated pneumococcal superinfection

“…Thorough investigation into co-infections is crucial as they can lead to severe clinical manifestations across all age groups, but particularly in elderly individuals, infants, young children, and the immunocompromised ( 11 , 28 ). Although influenza vaccination has proven to decrease hospitalization rates for pneumonia patients ( 29 ), and immunization against Spn has greatly reduced the incidence of invasive pneumococcal disease ( 30 , 31 ), the vaccines for Spn and IAV offer protection against single infections however ( 32 , 33 ), they have shown limited protection against co-infection in mice ( 34 – 36 ). Present treatments for these co-infections consist of antibiotic therapy aimed at Spn and antiviral medications targeting viruses.…”

A conserved antigen induces respiratory Th17-mediated serotype-independent protection against pneumococcal superinfection

“…There are more than 100 known serotypes of S. pneumoniae 9 and the rapid switching between serotypes, serotype displacement and appearance of non-typeable clinical isolates reduces the efficacy of CPS-based vaccines 10,11 . Importantly, CPS-based vaccines provide poor protection during pneumococcal superinfection following influenza in mice 12,13 . While CPS-based vaccines have shown great protection from IPD caused by serotype-matched pneumococcal strains and likely also contribute to protection following influenza infection, how well they work in this context is unclear from current human vaccine studies 14 .…”

“…While CPS-based vaccines have shown great protection from IPD caused by serotype-matched pneumococcal strains and likely also contribute to protection following influenza infection, how well they work in this context is unclear from current human vaccine studies 14 . What is clear is that influenza infection contributes to decreased pneumococcal clearance and increased lung injury even in PPSVvaccinated mice 13 . Conversely, pneumococcal colonization may also impede mucosal immune responses to live attenuated influenza vaccine, including reduced IgA in the nasal cavity and reduced IgG in the human lung 15 .…”