Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations

Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized

Exploring the therapeutic efficacy of glioma vaccines based on allo- and syngeneic antigens and distinct immunological costimulation activators

The efficacy of a various immunotherapeutic immunisation strategies for malignant glioma brain cancer was evaluated in the syngeneic CNS-1 Lewis rat glioma model. A prototype glioma cancer vaccine, which was composed of multivalent antigens derived from allogeneic and syngeneic cells and lysates, formed the prototype preparation of antigens. These antigens reflect the autologous antigens derived from the patient’s surgically removed tumor tissue, as well as allogeneic antigens form glioma tumor tissue surgically removed from donor patients. This antigen mixture provides a broad spectrum of tumor associated antigens (TAA) and helps to prevent escape of tumor immune surveillance when given as a vaccine. This antigen preparation was administered in a therapeutic setting with distinct single or multiple co-stimulation-favouring immunostimulants and evaluated for inhibition of tumor growth. Our prototype vaccine was able to arrest progression of tumor growth when co-delivered in a specific regimen togetherwith the costimulating multi-TLR agonist, Bacille Calmette Guerin (BCG) and interleukin-2, or with the Toll-Like receptor (TLR) 7/8 activator resiquimo

Rationales for including adjuvants in vaccines

The majority of vaccine antigens in the industry pipeline are relatively poor inducers of adaptive immunity unless effective adjuvants are coadministered. Adjuvants based on aluminium salts have been the only approved and available adjuvant for almost a century. However, although alum effectively promotes humoral immunity, it is not effective for diseases where cell-mediated immunity is required for protection. Moreover, other particulate adjuvants are superior to alum in promoting antibody responses to pandemic influenza antigens. There has been considerable progress in the discovery of novel antigens, which is facilitating vaccine development for currently intractable and new diseases, including therapeutic indications. Hence, especially when cell-mediated immune responses are required, these antigens demand a new generation of adjuvant, which can drive and specifically direct the desired immune responses. In parallel, increased understanding of immunology and, particularly, innate immune sensing is informing vaccine adjuvant research and driving the development of novel and specifically targeted vaccine strategies. In this concise chapter we address the importance of adjuvants in the important field of modern vaccine developmen

Conference Scene: Recent advancements in immunopotentiators for modern vaccines

Vaccines have proved to be the most successful preventive measure against a variety of infectious diseases. Owing to the potential safety concerns associated with the use of live-attenuated or killed pathogens, there is currently a drive to discover defined subunits of pathogens or recombinant molecules for new vaccines. The development of safe and potent vaccine adjuvants with the ability to enhance and direct broad and durable immune responses to these otherwise poorly immunogenic antigens is hence a top priority. The 4th International Conference on Immunopotentiators in Modern Vaccines, held in Porto, Portugal, 6–8 April 2011, offered an international forum for reviewing the current status of research and development, as well as application of novel immunopotentiators and vaccine adjuvants to vaccines. During the 3-day meeting, a stimulating and diverse mixture of presentations were presented. This report attempts to highlight a selected number of presentations of this meetin

Trends in vaccine adjuvants

Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a century and have been particularly effective at promoting protective humoral immunity. However, alum is not optimally effective for diseases where cell-mediated immunity is required for protection. Furthermore, adjuvants including oil-in-water emulsions have shown improved efficacy for avian influenza protection suggesting that even for diseases where humoral immunity can confer protection, there is scope for developing improved adjuvants. There have been major developments in antigen discovery over the past decade, which has accelerated the vaccine development process for new indications and this demands a new generation of adjuvants that can drive and specifically direct the desired immune responses. A number of systems are under investigation that combine different types of adjuvants into specific formulations with greater activity. Additionally, targeting of vaccines to specific immune cells shows great promise. In the case of cancer and chronic infectious diseases, it may be difficult to develop effective vaccines without blocking immune regulatory pathways, which impede cell-mediated responses. However, increased understanding of immunology and particularly the innate immune system is informing vaccine adjuvant research and consequently driving the development of novel and specifically directed vaccine adjuvant strategies. In this article we address the importance of adjuvants in vaccine development, the known mode of action of specific adjuvants and recent developments in this important fiel