Differential localization and function of antibody-forming cells responsive to inactivated or live-attenuated influenza virus vaccines

Currently, there are two different types of licensed influenza virus vaccines available in the USA, the live attenuated cold-adapted vaccine and the inactivated vaccine. Children greater than 2 years of age and adults younger than 50 years (apart from those suffering from immunodeficiencies or lung disease) may choose between the two vaccines. Previous studies have shown that both vaccines elicit significant serum antibody responses. However, comprehensive analyses of antibody-forming cells (AFCs) in the upper respiratory tract (URT), the critical site of pathogen entry, have been lacking. We therefore compared influenza virus-specific antibody and AFC activities in systemic and mucosal tissues following immunizations of cotton rats with inactivated or live-attenuated vaccines, including vaccines from the 2009-10 and 2010-11 seasons. Results demonstrated that inactivated and live-attenuated vaccines induced virus-specific AFCs, but patterns of residence and function were highly disparate. The inactivated vaccine elicited AFCs predominantly in the spleen and bone marrow; IgG was the main isotype. In contrast, the live attenuated vaccine elicited acute and long-sustained AFC responses in the diffuse nasal-associated lymphoid tissue (d-NALT) and lung, with IgA being the predominant isotype. The appearance of these d-NALT URT responses was confirmed by a similar study of the 2009-10 live attenuated vaccine in ferrets. Data emphasize that the inactivated and live-attenuated vaccines that are each capable of protecting humans from influenza virus disease do so by very different modes of immune surveillance.