Wanted, dead or alive: New viral vaccines

Abstract

Vaccination is one of the most effective methods used for protecting the public against infectious disease. Vaccines can be segregated into two general categories; replicating vaccines (i.e., live, attenuated vaccines) and non-replicating vaccines (e.g., inactivated or subunit vaccines). It has been assumed that live attenuated vaccines are superior to non-replicating vaccines in terms of the quality of the antiviral immune response, the level of protective immunity, and the duration of protective immunity. Although this a prevalent viewpoint within the field, there are several exceptions to the rule. Here, we will explore the historical literature in which some of these conclusions have been based, including “Experiments of Nature” and describe examples of the efficacy of replicating vaccines compared to their non-replicating counterparts. By building a better understanding of how successful vaccines work, we hope to develop better “next-generation” vaccines as well as new vaccines against HIV – a pathogen of global importance for which no licensed vaccine currently exists.

Vaccinomics and a New Paradigm for the Development of Preventive Vaccines Against Viral Infections

“…The control of latent viral infections [including cytomegalovirus (CMV), varicella zoster virus (VZV), Epstein-Barr virus (EBV), and Herpes Simplex virus (HSV)] is associated with cell-mediated immune responses, indicating that measures of cellular immunity should make ideal correlates of protection for these diseases. Advances in critical elements of vaccinomics (pathogen biology, epitope identification, and host response) have furthered our understanding of key targets of protective immunity, critical gene and pathways activated during immune responses, and appropriate endpoints and measures of clinical efficacy, thereby opening the door to improving current vaccines and creating next-generation vaccines against difficult pathogens such as tuberculosis, francisella, plague, malaria, subunit-based vaccines and, just as importantly, improved measures of protection and vaccine efficacy (Amanna and Slifka, 2009;de Boer et al, 2010;Vaine et al, 2010).…”

Discovering naturally processed antigenic determinants that confer protective T cell immunity

“…The majority of current vaccines consists of live, attenuated, or inactivated pathogens that were developed in the past by empirical approaches (1). Understanding vaccine-mediated correlates of immunity is critical for the rational design of novel pathogen-free vaccines against diseases caused by complex pathogens -such as malaria, tuberculosis, or HIV/AIDS, for which no effective vaccine currently exists -or to improve the safety and/or efficacy of existing vaccines (1)(2)(3)(4)(5)(6).…”

Current trends in West Nile virus vaccine development

“…Licensed human vaccines for flaviviruses include formaldehyde-inactivated vaccines against TBEV and JEV as well as a live, attenuated vaccine against YFV. Although cellular immunity plays an important role in clearing primary WNV infection [5-9], memory CD8 + T cells are dispensable if high levels of antiviral antibody are present [7] and vaccine-induced memory T cells may not play a substantial role in controlling flavivirus infection in humans [10]. Moreover, a number of studies using passive immunization have shown that transfer of neutralizing antibodies to naïve animals is sufficient for protection against lethal WNV infection [11-15].…”