ABSTRACT

Background image: Vaccine & Infectious Disease Organization

The use of vaccines dates back to Jenner and Pasteur, who first described the concept of vaccination more than 200 years ago. Since then, vaccines have been used successfully in humans and animals, and aside from clean water represent the most effective means of controlling systemic, respiratory, and gastrointestinal infections in both humans and animals.

Adjuvants are important components of vaccines. They provide an additional stimulus for the immune system, which typically results in stronger immune responses, and can assist in delivering or even targeting of the vaccine. Adjuvants represent a wide variety of molecules and formulations including cell-wall components, alum, QuilA, immunostimulatory complexes (ISCOMs), carbomers, liposomes, and oil-in water emulsions, to name a few. Many of these adjuvants have been developed empirically without an exact understanding of their mechanisms of action. Recent research, however, has provided insight into the activation of the immune system by pathogen recognition receptors, including toll like receptors, C-type lectins, mannose-receptors, and nucleotide-binding oligomerization domain (NOD)-like receptors. These receptors typically recognize highly conserved molecular pattern in pathogens such as bacterial DNA, lipopolysaccharide, or flagellin^1,2 and activation often leads to increased NF-κB and/or type I interferon (IFN) production, which can result in up-regulation of chemokines and cytokines needed for a variety of immune functions including recruitment of immune cells to the site of immunization, activation and maturation of dendritic cells, and improved presentation of the antigen.^3–5 These events constitute the innate immune response phase, which serves to 1.) contain and eradicate pathogens, and 2.) induce an appropriate adaptive immune response to eliminate infection and prevent reccurrence. Thus, by signaling through pathogen recognition receptors, adjuvants can stimulate both innate and acquired immunity resulting in stronger and longer lasting immune responses to vaccination.

Immune responses elicited by vaccines can be divided into innate and acquired immune responses. Innate immune responses occur within hours of infection or vaccination and are characterized by upregulation of chemokines and cytokines, typically providing a pro-inflammatory environment at the site of immunization. Other innate immune molecules include host defense peptides, also called cationic antimicrobial peptides, complement, and acute phase proteins, which together can recruit and activate dendritic cells to provide a link with the acquired immune response.⁵ The latter is characterized by the presence of antibodies and cytotoxic T cells, both of which are highly antigen-specific and which recognize very specific structures of the pathogen.

While vaccination in the past traditionally has focused on the induction of the acquired immune response, more recent approaches are focused on stimulating both innate and acquired immunity. In fact, it has become clear now that the innate immune response sets the stage for the acquired immune response, and thus, novel immunomodulators are being used as vaccine adjuvants that can link both innate and specific immunity to enhance the immune responses following vaccination.

Vaccination of the Newborn

Enhancing and modulating immune responses is particularly important in neonates, as infants and young children are highly susceptible to many diseases. When compared to the adult immune system, the neonatal immune system displays a number of functional differences, including its bias towards a Th2-type immune response, delayed germinal center development, shorter lifespan of plasma cells, fewer T-helper cells, and functionally impaired antigen-presenting cells. Together, these functional differences represent a great challenge for the development of effective vaccines for the newborn. Furthermore, potential interference with maternally-derived antibodies makes most vaccines less effective in the neonate.