Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice

Abstract

Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection.

Influenza vaccines to control influenza-associated bacterial infection: where do we stand?

“…Placebo-controlled <5 50.9% (not included) Turkey [101] Placebo-controlled (pooled data) <7 10.9% (1.3-19.7) Multinational [105] IIV-controlled (pooled data) <6 9.1% (-0.7-17.9) Multinational [105] Case-control 17-35 0.34 (0.29-0.40) ‡ USA looked at the bacterial load in the respiratory tract [110]. Remarkably, they showed that after vaccination with LAIV, there was an increase in bacterial density and duration of colonization in the upper respiratory tract, and this for up to 4 weeks after vaccination.…”

The Upper Respiratory Tract as a Microbial Source for Pulmonary Infections in Cystic Fibrosis. Parallels from Island Biogeography

“…Emigration of oral microbes to the lower airways due to aspiration is important in a number of respiratory conditions, in which a large fraction of infections are believed to have oral microbial etiology (35)(36)(37)(38)(39). Respiratory conditions associated with decreased extinction of microbes that reach the lower airways include smoking (31), vaccination and probiotics (40,41), respiratory virus infection (42)(43)(44), pneumonia (36), HIV (45,46), COPD (30,(47)(48)(49), and CF (50). In addition, improvements in oral hygiene practices in hospitals have been shown to prevent pneumonia (51).…”

Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

“…It is reported that vaccine-induced immunity to influenza virus can limit the mortality rate caused by secondary pneumococcal infection after influenza (17). While vaccinating mice with live attenuated influenza vaccine (LAIV) can reduce pneumococcal carriage after influenza virus infection (18), receiving LAIV can, on the other hand, enhance pneumococcal colonization in the absence of influenza virus infection (19). Previous studies highlighted the complexity of the interaction between LAIV and pneumococcal carriage and suggested the importance of anti-influenza virus antibody to control the dual attack by influenza virus and pneumococcus.…”