The baboon model of pertussis: effective use and lessons for pertussis vaccines

Abstract

The USA is experiencing a pertussis resurgence that resulted in a 60-year high of 48,000 cases in 2012. Our ability to counteract this resurgence is hampered by the fact that pertussis pathogenesis and immunity to pertussis infection are not well studied. Studies in humans are difficult due to the low frequency of pertussis in the population, the cyclical nature of incidence and the sporadic geographic distribution of cases. While existing animal models reproduce many aspects of pertussis, none of them adequately reproduces the full spectrum of disease. We describe the baboon model of pertussis. The baboon model is the first animal model that recapitulates the full spectrum of human pertussis including coughing and transmission. This model is being utilized to examine pertussis pathogenesis and host responses to infection and vaccination. It is likely the baboon model will provide an important tool in the development of improved pertussis vaccines.

Keywords::

• baboons
• pertussis
• T-cell memory
• Th17
• vaccines
• whooping cough

Financial & competing interests disclosure

The authors’ salaries are supported in full by the US FDA. The authors have no other 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 apart from those disclosed.

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

Key issues

• Despite widespread vaccine coverage in the USA, pertussis incidence has been increasing at an alarming rate.

• The lack of an animal model that fully replicates the human disease has limited our understanding of pertussis pathogenesis and hampered our ability to respond to this important public health concern.

• A baboon model for pertussis was recently developed that closely matches the clinical illness, including development of paroxysmal cough and demonstration of host-to-host transmission by aerosolized respiratory droplets.

• Acellular pertussis vaccination in baboons induces a Th2-skewed immune response and prevents pertussis-associated symptoms but does not prevent mucosal colonization or host-to-host transmission.

• Infection by live Bordetella pertussis and whole-cell vaccination induce immune responses that are characterized by Th17 memory and provide protection from colonization.

• These data suggest that acellular-vaccinated people are a possible reservoir for B. pertussis circulation and that Th17 responses may be required to prevent B. pertussis colonization.

• In the future, the baboon model will be useful for unraveling some of the mysteries of pertussis pathogenesis and as a pre-clinical tool for evaluating novel pertussis vaccines.