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.

Keywords::

• carriage
• decolonization
• immune evasion
• Staphylococcus aureus
• vaccine

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Staphylococcus aureus infections do not provide immunization. This pathogen is able to suppress host immune response. The development of an effective vaccine is therefore a challenge.

• • The polymorphism in the expression of its virulence factors and its antigens lead to difficulties in characterization of stable proteins of interest.

• • Targets of prior vaccine trials have probably been inadequate, leading to only a humoral response. The role of cellular response in immunity against S. aureus is now well demonstrated.

• • The carriage of S. aureus has probably been neglected during prior vaccine clinical trials. The carriage should be studied and at least analyzed in the future clinical trials, as it is a crucial step in the S. aureus infection.

• • There is greater feasibility in conducting clinical vaccine trials in carriers. Indeed, persistent carriers, the population with higher risk to develop infection, are plentiful and their identification is quite easy. This validation step in persistent carriers would be a prerequisite before conducting larger trials for S. aureus vaccines.

Notes