This issue reviews the performance of vaccines in challenging environments, summarises current views on the reasons why some vaccines work less well for some children or populations and considers what approaches are necessary to understand why such differences can occur, so that overall vaccine efficacy can be optimised for all.
Vaccinating against infectious diseases saves over 2.5 million lives annually. Additional vaccines are still needed for major causes of morbidity and mortality, such as HIV and malaria. At current levels of vaccination coverage, an estimated 4–19 million children born each year (3–13% of the birth cohort) receive routine vaccines against childhood infections, such as diphtheria, pertussis, tetanus and measles, but some remain unprotected as a result of limited vaccine effectiveness. This figure stands at 77 million for vaccination with bacille Calmette–Gue´rin (BCG) against tuberculosis (TB), and currently 10 and 5 million for invasive pneumococcal disease and rotavirus gastroenteritis, respectively.

The focus of this issue of the Philosophical Transactions of the Royal Society, based on a Discussion Meeting held at the Royal Society in November 2014, is on the lessons learned from individual variation in vaccine response with regard to protective immunological mechanisms and the implications for vaccine design.

 Oral vaccines as a special case

Only a few commercial oral vaccines are currently available, against poliovirus, rotavirus, cholera and typhoid, and only oral poliovirus and rotavirus vaccines are widely used in national immunisation programmes. Over the past five decades, since oral vaccines were first introduced, experience in developing countries has shown that immune responses to oral vaccines may be lower and less consistent than in most industrialised countries.

Human genetic and environmental determinants of vaccine response

The immune response to vaccination in children may be determined by their individual characteristics such as age, nutritional status and genome, as well as environmental factors such as infection history or exposure to maternal antibodies and antigens in breast milk.

Studies on the immunology of malnutrition using modern laboratory methods are largely absent and represent an important research need.  Co-infections or seasonality have also shown to play a role and a number of large studies are currently under way to determine the impact of human genetics on vaccine responses.

 What should we measure in vaccine studies?

To comprehend why certain vaccines fail to protect certain individuals remains a challenge, which is amplified in the context of vaccines required to induce cell-mediated immunity in order to achieve protective efficacy, as for TB, HIV or malaria. The absence of clear correlates of protection continues to hamper the successful development of such vaccines. The concept of Systems Vaccinology, where insights into immune mechanisms of protection can be gathered during the conduct of clinical trials by subjecting samples to in depth analysis of gene expression might be useful in this context.

The Vaccines & Immunity Theme researchers from MRC Unit The Gambia are already contributing to this area of work, as part of an ongoing effort to describe an emerging paradigm in vaccine research where discovery begins with detailed, typically high-throughput, and immunological investigation in humans following vaccination or infection.

The main reasons for diversification in immune responses are illustrated and summarised in the paper by Kampmann& Jones which focuses on innate and vaccine responses in early infancy which highlighted variation in the immune response among humans as a key part of the diverse vaccine responses that can be measured with laboratory assays currently in use http://www.mrc.gm/profile/beate-kampmann/, Theme Leader of Vaccines and Immunity, co-organiser of the meeting at the Royal Society and senior author of 2 of the resulting publications in the commissioned special edition of the proceedings from the meeting said: “It has been a pleasure to spend 4 days of intense deliberations from all angels to discuss why not all vaccines might be working equally well in all settings. We have come away with many clues and also some very good ideas how to nail these questions using the exciting new technologies and “big data” capabilities now at our disposition. We hope that the meeting and the interactions between the over 100 international participants and leading experts in the field can shape the research agenda in this area and lead to even better vaccines to be implemented across the world. Our research at the MRC Unit is already playing a key role on this journey”

This article was first published on Royal Publishing website: http://www.mrc.gm/profile/beate-kampmann/