An evaluation of the emerging vaccines and immunotherapy against staphylococcal pneumonia in children

Abstract

Background: Staphylococcus aureus is a commensal of human skin and nares. It is also one of the leading nosocomial pathogens in both developed and developing countries and is responsible for a wide range of life threatening infections, especially in patients who are immunocompromised, post-surgery, undergoing haemodialysis and those who are treated with catheters and ventilators. Over the past two decades, the incidence of nosocomial staphylococcal infections has increased dramatically. Currently there are at least seven vaccine and immunotherapy candidates against S. aureus in the developmental phase targeting both active and passive immunization.

Methods: We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against Staphylococcus aureus relevant to several criteria of interest: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies) to participate. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%.

Results: The panel of experts expressed low levels of optimism (score around or below 50%) on the criteria of answerability, efficacy, maximum disease burden reduction potential, low cost of production, low cost of implementation and affordability; moderate levels of optimism (scores around 60 to 80%) that these vaccines could be developed at a low cost, and thus on the deliverability, sustainability and impact on equity; and high levels of optimism (scores above 80%) regarding acceptable of such a product to both the end-users and health workers. While assessing the candidates for passive immunization against S.aureus, the experts were poorly optimistic regarding low production cost, low implementation cost, efficacy, deliverability, sustainability, affordability and equity; moderately optimistic regarding answerability and acceptability to health workers and end-users. They were of the opinion that these interventions would have only a modest impact (3 to 5%) on the burden of childhood pneumonia. .

Conclusion: In order to provide an effective vaccine against S. aureus, a number of unresolved issues in vaccine development relating to optimal antigenic target identification, criteria for acceptable efficacy, identification of target population, commercial development limitations, optimal timing of immunization strategy, storage, cold chain requirements and cost need to be addressed properly. There is still a great deal unknown about the complex interaction between S. aureus and the human host. However, given the nature of S. aureus and the lessons learned from the recent failure of two emerging vaccines, it is clear that a multi-component vaccine is essential. Combating only one virulence factor is not sufficient in the human host but finding the right combination of factors will be very challenging.

Figure 1

A summary of Stage I of the CHNRI process of evaluation of an emerging intervention (a systematic review of the key CHNRI criteria). CHNRI- Child Health and Nutrition Research Initiative

Figure 2

A summary of Stage II of the CHNRI process of evaluation of an emerging intervention (an expert opinion exercise using the CHNRI criteria). CHNRI- Child Health and Nutrition Research Initiative

Figure 3

The current status of the research into Staphylococcal vaccines presented to the expert group for stage II of the CHNRI process

Figure 4

The current status of the research into passive immunization against S. aureus presented to the expert group for stage II of the CHNRI process

Figure 5

The results of Stage II CHNRI process – an expert opinion exercise assessing the potential usefulness of investment in staphylococcal vaccines. CHNRI- Child Health and Nutrition Research Initiative

Figure 6

The results of Stage II CHNRI process – an expert opinion exercise assessing the potential usefulness of investment in passive immunization against S.aureus. CHNRI- Child Health and Nutrition Research Initiative