Induction of B cell immunity in the lung mucosa

ended

Vaccination is widely considered one of the greatest medical achievements for preventing infectious diseases. The basis for most currently licensed human vaccines relies on the induction of high affinity antibodies by antigen-specific B cells that can neutralise pathogens in case of future exposures. The widespread immunity that vaccination conveys has led to worldwide eradication of smallpox and the elimination of diseases such as polio, diphtheria, and tetanus from most parts of the world. In spite of the worldwide effort to generate a universal flu vaccine, the induction of long-lasting protective immunity has been, so far, unsuccessful owing to the rapid antigenic variation of influenza virus. Due to these limitations, influenza infection remains a serious threat to public health and economy, with 5 to 30% of the world population acquiring seasonal influenza virus every year. Interestingly, it was recently shown that antibodies derived from lung-resident germinal centre B cells, unlike those arising from lymph nodes or spleen, bear the ability to neutralise different strain variants of the virus. These findings not only uncover the physiological advantage of tissue-specific germinal centres but also underscore the potential of targeting B cells directly at the lung mucosa to generate protective vaccines against highly variable viruses. My research plan aims to unveil the early events involved in the induction of B cell immunity at the lung mucosa, with a focus on how respiratory antigens are delivered to B cells at the barrier surface. A precise delineation of the initial steps required for the generation of broadly-neutralising antibodies upon respiratory infection will provide invaluable medical insights towards the development of a universal flu vaccine.