Vaccine 33S (2015) B40–B43 Contents lists available at ScienceDirect Vaccine j o ur na l ho me page: www.elsevier.com/locate/vaccine Review Gaps in knowledge and prospects for research of adjuvanted vaccines Robert Seder a , Steven G. Reed b,* , Derek O’Hagan c , Padma Malyala c , Ugo D’Oro d , Donatello Laera d , Sergio Abrignani e , Vincenzo Cerundolo f , Lawrence Steinman g , Sylvie Bertholet d a Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA b Infectious Disease Research Institute, Seattle, WA, USA c Novartis Vaccines, Cambridge, MA, USA d Novartis Vaccines, Via Fiorentina 1, Siena, Italy e Instituto Nazionale Genetica Molecolare, Milano, Italy f Oxford University, Oxford, England, United Kingdom g Stanford University, School of Medicine, Palo Alto, CA, USA a r t i c l e i n f o Keywords: Vaccine Adjuvant a b s t r a c t A panel of researchers working in different areas of adjuvanted vaccines deliberated over the topic, “Gaps in knowledge and prospects for research of adjuvanted vaccines” at, “Enhancing Vaccine Immunity and Value” conference held in July 2014. Several vaccine challenges and applications for new adjuvant technologies were discussed. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction From a historical perspective, vaccines have been instrumental in eradicating or drastically reducing the incidence of numerous dreaded infectious diseases such as small pox, polio, tetanus, diphtheria, cholera, rabies and typhoid [1]. Vaccines to combat two major deadly infections, human papillomavirus [2] and meningococcal disease [3], were also introduced in the recent past, and ongoing research aims to eliminate many more diseases. The need for optimizing adjuvant formulations for new vaccines presents a number of challenges, though for most of these paths forward are becoming evident. This workshop addressed issues and potential solutions focusing on developing vaccines for HIV, malaria, tuberculosis (TB), and cancer. Although certain challenges are specific for each of these vaccine targets, some basic issues hold constant. These include adjuvant access, the importance of formulation, and the need for adjuvants that promote appropriate T cell responses, whether as effectors or helpers of effective and durable antibody responses. A radical change has taken place in the evolution of vaccines since Edward Jenner’s inoculation of cowpox matter as a small pox vaccine in the 1800s in an eight-year-old boy [4]. This seminal example using an attenuated viral vaccine to elicit long lived and broad based humoral and cellular immunity highlights the * Corresponding author. Tel.: +1 206 381 0883. E-mail addresses: sreed@idri.org, steve.reed@idri.org (S.G. Reed). efficiency by which antigens and innate immunity induced by the virus delivered synchronously is so effective. Since this discovery many vaccine approaches have become more selective where the science has emerged to encompass antigens in the form of conjugates, toxoids and recombinant vectors, inactivated and live attenuated vaccines and subunit vaccines [5]. In terms of proteins or inactivated viral productions, adjuvants have been used to improve the efficiency, potency and durability of immune responses [6]. There is extensive history of the use of vaccine adjuvants, mostly inadvertently through the inclusion of natural products in the form of live or inactivated virus or microbial products, but more recently through intentional efforts to develop vaccine components to enhance immune responses. Two such com- ponents in wide use are aluminum salts, commonly referred to as alum, and oil in water emulsions such as MF59 [7]. In addition to the empirical first generation adjuvants such as Alum, MF59 and AS03 emulsions, second generation adjuvants are typically agonists of toll like receptors (TLRs) and act by triggering signal transduction pathways that lead to activation of innate and adaptive immune cells. Though widely used as standalone adjuvants, both alum and emulsions may be used with TLR (and other) ligands as important formulation components. The most advanced example of this is the TLR4 ligand MPL ® which has been combined with alum in the GSK Cervarix ® vaccine [8]. MPL ® is purified from endotoxin (lipopolysaccharide, LPS) derived from Gram-negative bacteria [9]. Endotoxin has been known as a potent stimulus of antibody responses, and exten- sive biochemical, biophysical, and immunological studies were http://dx.doi.org/10.1016/j.vaccine.2015.03.057 0264-410X/© 2015 Elsevier Ltd. All rights reserved.