Molecular adjuvants for mucosal immunity

Abstract

Mucosal surfaces represent the entry route of a multitude of viral pathogens. For many of these viruses, such as the herpes simplex viruses and human immunodeficiency virus, no effective vaccine exists. Hence, it is important that prospective vaccines engender maximal immunity at these susceptible sites. Genetic vaccines encoding adjuvant molecules represent one approach to optimize mucosal as well as systemic immunity. Promising candidates include various inflammatory cytokines and chemokines that might be used to enhance the primary response to a level sufficient for protection. Encouraging studies involving cytokines such as granulocyte/macrophage colony-stimulating factor, interleukin-2 (IL-2), IL-12, IL-18, and many others are examined. Notable chemokines that may offer hope in such efforts include IL-8, RANTES, CCL19, CCL21, and a few others. Combinatorial approaches utilizing several cytokines and chemokines will most likely yield the greatest success. In addition, as more is discovered regarding the requirements for memory development of T cells, boosters involving key cytokines such as IL-15 and IL-23 may prove beneficial to long-term maintenance of the memory pool. This review summarizes the progress in the use of genetic vaccines to achieve mucosal immunity and discusses the needed strategies to maximize long-term prospective immunity at this vulnerable entry site.

Classical swine fever virus replicon particles lacking the Ernsgene: a potential marker vaccine for intradermal application

“…Currently new tools are being developed for convenient, needle-free intradermal vaccination, for example Vet Jet TM (Merial Limited, Duluth, GA, USA) or PowderJect ND5.2 TM delivering system (PowderJect vaccines, Inc., Middleton, USA). An improvement of VRP vaccines can also possibly be achieved by inclusion of genes encoding cytokines or chemokines in the replicon [30].…”

Live Attenuated Influenza Virus Expressing Human Interleukin-2 Reveals Increased Immunogenic Potential in Young and Aged Hosts

“…IL-2 plays a crucial role in the stimulation and maturation of the immune system and is frequently used as a vaccine supplement or genetic adjuvant (1,4,9,16,34,37,38,52,62). For this reason, we compared the immunogenicities of the attenuated influenza ca Sing virus and a modified variant which expresses biologically active IL-2 in young adult and aged mice.…”

“…Utilization of human interleukin-2 (IL-2) as a vaccine supplement resulted, for example, in enhanced immunogenicity and protection efficacy of the inactivated influenza vaccine not only in young but also in aged hosts (1,4,5,37). The beneficial immunomodulating effect of IL-2 on the immune system could also be demonstrated when IL-2 was encoded by different viral vectors, virus-like particles, or DNA candidate vaccines in approaches aimed at combating infectious diseases or in antitumor therapy programs (9,16,34,38,62).…”

Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus

“…Cytokines are key molecules that trigger the innate and adaptive immune responses (including maturation of Ag-presenting cells, differentiation of Th1 and Th2 cells, and induction of cytotoxic natural killer [NK] cells and CTLs), resulting in protective layers against virus infection (11,41,43). Therefore, cytokines are promising vaccine adjuvants for enhancing the immune response against infectious pathogens.…”