Proteomic contributions to our understanding of vaccine and immune responses

Abstract

Vaccines are one of the greatest public health successes; yet, due to the empirical nature of vaccine design, we have an incomplete understanding of how the genes and proteins induced by vaccines contribute to the development of both protective innate and adaptive immune responses. While the advent of genomics has enabled new vaccine development and facilitated understanding of the immune response, proteomics identifies potentially new vaccine antigens with increasing speed and sensitivity. In addition, as proteomics is complementary to transcriptomic approaches, a combination of both approaches provides a more comprehensive view of the immune response after vaccination via systems vaccinology. This review details the advances that proteomic strategies have made in vaccine development and reviews how proteomics contributes to the development of a more complete understanding of human vaccines and immune responses.

Keywords: Systems biology; Vaccine; Vaccinology.

Figure 1

Overview of the immune response after a vaccine is given. Vaccines mimic the natural infection. The innate immune system, comprised of macrophages, dendritic cells, natural killer cells, and neutrophils work through pattern recognition receptors on their surfaces to recognize pathogen-associated molecular patterns. These cells recruit other cells to the area and work for approximately three days to clear the antigen through endocytosis. Between days 3 and 7, antigen presenting cells help activate B and T cells by presenting antigen specific peptides. The adaptive immune response is specific to the antigen being fought. B cells secrete antibodies against the antigen, and cytotoxic T cells kill infected cells. B and T cells can become memory cells, which continuously circulate throughout the blood until reinfection. Memory immunity is the ultimate goal of vaccines. Cell icons reproduced from Janeway’s Immunobiology by Murphy, Kenneth; et al with permission of Garland Science via Copyright Clearance Center.

Figure 2

General outline of the vaccine development and production process highlighting areas where proteomics is used.

Figure 3

Ribbon model of a monomer of the influenza hemagglutinin protein. Blue represents the HA1 portion, and the green is the HA2 portion. HA1 contains the receptor-binding domain and is the main target of the immune responses. HA2 is the anchor of the virus and is responsible for the fusion of the envelope and cellular endosomal membranes.

Figure 4

Overview of systems vaccinology methods. Systems vaccinology aims to collect and integrate data from all components of the immune response. A combination of standardized immune serologic assays with the high-throughput transcriptomic, proteomic, and metabolomic measurements will provide the opportunity to predict immunologic protection from vaccines. [153]. Reprinted from Seminars in Immunology, 25, Li, S. et al., Systems biological approaches to measure and understand vaccine immunity in humans, 209–218, 2013, with permission from Elsevier.