Is there a potential for novel, nasal pertussis vaccines?

ABSTRACT

Introduction

Pertussis, caused by Bordetella pertussis, remains a major public health problem, despite high vaccination coverage. Furthermore, the disease incidence has increased recently, especially in countries that have switched from whole-cell to acellular pertussis vaccines.

Areas covered

Here, we provide a state-of-the art summary of the reasons for the pertussis resurgence and discuss potential solutions using current vaccines and challenges for the development of novel vaccines. PubMed was searched for publications with the terms pertussis and vaccines. Many new vaccine candidates are proposed but most have not reached clinical development. Most of them induce strong systemic immune responses and protection in mice. However, since B. pertussis is a mucosal pathogen, albeit with systemic effects, local immunity may be crucial to prevent B. pertussis infection and transmission. Recent efforts have focused on vaccine candidates able to induce immunity in the nasal cavity, and one of them is currently in clinical development.

Expert commentary

New pertussis vaccines are needed to durably control the disease and circulation of B. pertussis. A major challenge is to prove efficacy against disease in randomized controlled trials, while it is feasible to provide evidence for prevention of infection, since asymptomatic carriage of B. pertussis is wide spread.

KEYWORDS:

• Pertussis resurgence
• whole-cell vaccines
• acellular vaccines
• prevention of infection
• BPZE1

Article highlights

• Pertussis is re-emerging in many countries that have switched from whole-cell to acellular vaccines because of antigenic mis-matching between vaccine antigens and circulating strains, the fast waning of vaccine-induced immunity, and the failure of current vaccines to prevent B. pertussis infection and transmission.

• B. pertussis is a strictly respiratory mucosal pathogen, yet current vaccines induce potent systemic antibody and T cell responses but poor mucosal immunity.

• New pertussis vaccines should prevent both pertussis disease and B. pertussis infection/transmission, which may be achieved by vaccines that target the respiratory mucosa, especially in the nasal cavity. One such vaccines is currently in clinical development.

• Randomized placebo-controlled clinical efficacy trials are currently not feasible anymore. Therefore, the prevention of disease cannot be demonstrated using such trials. However, it is possible to demonstrate prevention of infection in randomized controlled trials, which might serve as a surrogate endpoint for prevention of disease, if accepted by regulatory agencies for licensure.

Declaration of interest

C Locht declares to be listed as an inventor on patents on BPZE1, which were licensed to ILiAD Biotechnologies. The author has 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded