The unprecedented increase of life expectancy challenges society to protect the elderly from morbidity and mortality making vaccination a crucial mean to safeguard this population. Indeed, infectious diseases, such as influenza and pneumonia, are among the top killers of elderly people in the world. Elderly individuals are more prone to severe infections and less responsive to vaccination prevention, due to immunosenescence combined with the progressive increase of a proinflammatory status characteristic of the aging process (inflammaging). These factors are responsible for most age-related diseases and correlate with poor response to vaccination. Therefore, it is of utmost interest to deepen the knowledge regarding the role of inflammaging in vaccination responsiveness to support the development of effective vaccination strategies designed for elderly. In this review we analyse the impact of age-associated factors such as inflammaging, immunosenescence and immunobiography on immune response to vaccination in the elderly, and we consider systems biology approaches as a mean for integrating a multitude of data in order to rationally design vaccination approaches specifically tailored for the elderly.

We developed a novel surface display system based on the use of bacterial spores. A protein of theBacillus subtilisspore coat, CotB, was found to be located on the spore surface and used as fusion partner to express the 459-amino-acid C-terminal fragment of the tetanus toxin (TTFC). Western, dot blot and fluorescent-activated cell sorting analyses were used to monitor TTFC surface expression on purified spores. We estimated that more than 1.5 × 10³TTFC molecules were exposed on the surface of each spore and recognized by TTFC-specific antibodies. The efficient surface presentation of the heterologous protein, together with the simple purification procedure and the high stability and safety record ofB. subtilisspores, makes this spore-based display system a potentially powerful approach for surface expression of bioactive molecules.

Here, we show that bacteria inducede novosynthesis of both major histocompatability complex (MHC) class I and II molecules in a mouse dendritic cell culture system. The neo-biosynthesis of MHC class I molecules is delayed as compared with that of MHC class II. Furthermore, bacteria stabilize MHC class I molecules by a 3-fold increase of their half-life. This has important consequences for the capacity of dendritic cells to present bacterial antigens in the draining lymph nodes. In addition, a model antigen, ovalbumin, expressed on the surface of recombinantStreptococcus gordoniiis processed and presented on MHC class I molecules. This presentation is 10⁶times more efficient than that of soluble OVA protein. This exogenous pathway of MHC class I presentation is transporter associated with antigen processing (TAP)-dependent, indicating that there is a transport from phagolysosome to cytosol in dendritic cells. Thus, bacteria are shown to be a potentially useful mean for the correct delivery of exogenous antigens to be presented efficiently on MHC class I molecules.

The human immune system and the microbiota co-evolve, and their balanced relationship is based on crosstalk between the two systems through the course of life. This tight association and the overall composition and richness of the microbiota play an important role in the modulation of host immunity and may impact the immune response to vaccination. The availability of innovative technologies, such as next-generation sequencing (NGS) and correlated bioinformatics tools, allows a deeper investigation of the crosstalk between the microbiota and human immune responses. This review discusses the current knowledge on the influence of the microbiota on the immune response to vaccination and novel tools to deeply analyze the impact of the microbiome on vaccine responses.

To circumvent the need to engineer pathogenic microorganisms as live vaccine-delivery vehicles, a system was developed which allowed for the stable expression of a wide range of protein antigens on the surface of Gram-positive commensal bacteria. The human oral commensal Streptococcus gordonii was engineered to surface express a 204-amino acid allergen from hornet venom (Ag5.2) as a fusion with the anchor region of the M6 protein of Streptococcus pyogenes. The immunogenicity of the M6-Ag5.2 fusion protein was assessed in mice inoculated orally and intranasally with a single dose of recombinant bacteria, resulting in the colonization of the oral/pharyngeal mucosa for 10-11 weeks. A significant increase of Ag5.2-specific IgA with relation to the total IgA was detected in saliva and lung lavages when compared with mice colonized with wild-type S. gordonii. A systemic IgG response to Ag5.2 was also induced after oral colonization. Thus, recombinant Gram-positive commensal bacteria may be a safe and effective way of inducing a local and systemic immune response.