Staphylococcal vaccine development: review of past failures and plea for a future evaluation of vaccine efficacy not only on staphylococcal infections but also on mucosal carriage

Abstract

Staphylococcal disease represents a universal burden including acute, life-threatening infections as well as chronic infections usually associated with foreign materials. Infections occur notably in permanent carriers of Staphylococcus aureus. To date, all the attempts to develop an efficacious vaccine against S. aureus have failed. Failures in vaccine clinical trials might be related to a focus on single targets and development of humoral-based vaccines rather than vaccines with a combination of antigens stimulating both humoral and cellular immunity. The end points of these unsuccessful trials were a reduction in mortality or bacteremia, whereas the patient's decolonization was not assessed. Adopting the latter point of view, the aim of this article is to discuss nasal mucosal decolonization as a complementary marker of vaccine efficacy for clinical research in vaccine development.

Four-Component Staphylococcus aureus Vaccine 4C-Staph Enhances Fcγ Receptor Expression in Neutrophils and Monocytes and Mitigates S. aureus Infection in Neutropenic Mice

“…The approaches used thus far to develop a vaccine against S. aureus infections have been unsuccessful (14) and the definition of new strategies to achieve this goal is an urgent priority (4,15). Development of an efficacious S. aureus vaccine appears to be a particularly challenging task since the pathogen has evolved to infect a variety of host microenvironments (1) and evade the immune system (16)(17)(18).…”

Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults

“…8 With the growing burden of S. aureus disease, increasing antibiotic resistance, and limited efficacy of decolonization protocols, 9,10 there is substantial interest in development of a S. aureus vaccine for use in high risk populations. Although an effective S. aureus vaccine remains elusive, [13][14][15][16][17][18] there is general consensus on a multi-antigen approach to vaccine development, which targets T and B cell responses to S. aureus cell surface components, virulence factors and toxins. 19 a-toxin and Panton-Valentine leukocidin (PVL) are 2 toxins of interest for a toxoid based approach that have shown efficacy in animal models.…”

From Immunologically Archaic to Neoteric Glycovaccines

“…Although conjugate vaccines are unable to prevent colonization, the immune system removes the covered serotypes using various effector mechanisms including antibody-mediated, Th1, and Th17 immune responses [57,58,59,60]. The Th17 response deserves a special note because it could provide a serotype-independent defence mechanism involving B cells and innate interleukin (IL)-17 [61].…”