The childhood disease whooping cough is caused by the Gram negative bacterium Bordetella pertussis.
Although there are effective vaccines, whooping cough is a major cause of disease and death in children worldwide.
The first vaccines against pertussis – comprising killed whole cells of pertussis (wP) – were developed in the 1920s and widely introduced in the 1940s. They proved effective and led to a rapid reduction in the incidence of whooping cough.
However, concerns about their safety resulted in their replacement in the 1990s with acellular vaccines (aP) that are composed of purified proteins from the bacterium.
Today both types of vaccines are in use, with aP used in developed countries while wP is still predominantly used in developing countries. Both forms are usually found in combination with diphtheria and tetanus vaccines along with other components.
Recent outbreaks of pertussis in countries with high aP coverage has highlighted the need for improved vaccines and continuing vigilance.
The pertussis group of NIBSC has 3 main functions – control testing, standardisation and research and development.
We maintain a diverse portfolio of 60 biological reference preparations used in the production, control and characterisation of pertussis containing vaccines. These include International Standards for pertussis antigens such as pertussis toxin.
There are also wP and aP reference vaccines.
We have an extensive range of anti-sera from humans, mice and rabbits against pertussis antigens. We also have an extensive list of monoclonal antibodies against a range of antigens commonly found in pertussis vaccines.
These standards cover a wide range of applications. Reference sera, monoclonal antibodies, vaccine international standards and purified B. pertussis antigens can be used as standards for regulatory assays.
Purified antigens and human sera are important reference reagents in the standardisation of diagnostic assays for epidemiology and vaccine studies.
The pertussis reference materials can also be used for a wide range of research applications such as investigating the mechanism of vaccine immunity and characterisation of existing and new vaccines.
We have wide experience of testing both whole cells of pertussis (wP) and acellular vaccines (aP) vaccines to ensure they are safe and offer protection.
We carry out scientific testing of aP containing vaccines as part of NIBSC’s role as a National Control Laboratory.
We also perform testing on wP vaccine for the World Health Organisation (WHO) to support the WHO Prequalification Programme.
We also develop new and improved assays for ensuring the quality of pertussis vaccines.
Our group’s control and standardisation activities are supported by a diverse programme of research and development. We are active in many research areas in the wider pertussis community.
These projects include investigating an increase in the number of pertussis cases leading to a significant number of deaths – despite widespread vaccine coverage – in the developed world in recent years. There has also been a change in the genetics of circulating strains. We are currently studying clinical isolates to determine if there is a difference in their pertussis toxin (PTx) activity.
We are committed to finding alternatives to the use of animals in batch release tests, and are actively researching alternatives to the histamine sensitisation test which is used to assure the safety of pertussis vaccines and which requires a large number of mice. Alternatives include a two-component in-vitro biochemicalassay that measures both the binding activity of active PTx and enzymatic component of active PTx that measures the catalytic region of the toxin. The use of a mammalian cell line (CHO cells) is also being developed as a method to measure active PTx. For wP we have refined and reduced the number of mice required for assuring vaccine potency.
Ensuring vaccine safety through a better understanding of its PTx’s mode of action is key to our research. Evidence suggests that active PTx has a detrimental effect on the integrity of the blood brain barrier (BBB), allowing toxins to access the brain and cause seizures. We are investigating the effect of PTx and possible interaction of PTx with other antigens on the BBB using a cell culture model that mimics the BBB. With a better understanding of the toxic effect of PTx, the aim is to develop an improved safety test that does not require animals.
Recent outbreaks of pertussis worldwide indicate that existing vaccines need to be improved. We have investigated a number of ways to improve aP vaccines from We are investigatingimproving stability and effectiveness through the use of protein-coated microcrystals as a means to potentially improve the stability and effectiveness of aP to alternative adjuvants that may increase the immune system’s responses to aP vaccination. Such adjuvants include .
We are also assessing the use of DNA regions called CpG as an adjuvant to improve aP vaccinesand fungal glucans.
Alternatives to the use of traditional aP vaccines for the prevention of whooping cough have also been studied. We have investigated the use of monoclonal antibodies for the prevention and treatment of B. pertussis infection. Viral vector-based vaccines may induce a more robust immune response and we’re currently assessing the ability of viral vectors expressing B. pertussis antigens to protect against infection.
We are studying alternative delivery methods such as direct application to the skin in the presence of a mild electric field as part of a collaboration. Our scientists collaborate with many UK, European and Global expert groups as part of different grant-funded consortia.
The pertussis group plays an important role in advising diverse organisations worldwide. For example, we advised the WHO in forming the recommendations to assure the quality, safety and efficacy of aP, wP and combination vaccines. We also advise on monographs for the European and United States Pharmacopoeias, along with giving support and advice to MHRA and vaccine manufacturers.
Kevin Markey, Principal ScientistCathy AsokanathanAlexandra Douglas-BardsleySharon Tierney
06/124: Monoclonal Antibody for Serotyping Bordetella pertussis Fimbrial Antigen 2 (1st International Standard) 06/128:Monoclonal Antibody for Serotyping Bordetella pertussis Fimbrial Antigen 3 (1st International Standard) 06/140: Pertussis Antiserum (human)(1st International Standard) 06/142: Pertussis Antiserum (Human) (1st WHO Reference Reagent) 76/522: Opacity 5IRP88/522: Bordetella pertussis (Whole cell vaccine) 3BRP 89/530: Anti-Bordetella pertussis serum (Human) 89/594: Bordetella pertussis (W28) LPS 2ug 89/596: Bordetella pertussis anti-agglutinogen 1(rabbit) 89/598: Bordetella pertussis anti-agglutinogen 2 (rabbit) 89/600: Bordetella pertussis anti-agglutinogen 3 (rabbit) 89/670: Bordetella pertussis (W28) LPS25ug 90/520: Bordetella pertussis, filamentous haemagglutinin (FHA) 94/532: Pertussis Vaccine (Whole Cell) 97/558: Bordetella pertussis anti 69kD serum (sheep) 97/564: Bordetella pertussis anti FHA serum (sheep) 97/572: Bordetella pertussis PT anti serum (sheep) 97/574: Bordetella pertussis anti Fim3 serum (sheep) 97/642: Bordetella pertussis anti serum (mouse) 1RR 99/506: Anti-PT S1 subunit Monoclonal Antibody (1B7) 99/508: Anti-PT S1 subunit Monoclonal Antibody (1D7) 99/510: Anti-PT S1 subunit Monoclonal Antibody (3F11) 99/512: Anti-PT S1 subunit Monoclonal Antibody (10D6) 99/514: Anti-PT S1 subunit Monoclonal Antibody (8G4) 99/516: Anti-PT S1 subunit Monoclonal Antibody (E1E) 99/518: Anti-PT S1 subunit Monoclonal Antibody (E2E) 99/520: Anti-PT S1 subunit Monoclonal Antibody (3F10) 99/522: Anti-PT S1 subunit Monoclonal Antibody (11D9) 99/524: Anti-PT S1 subunit Monoclonal Antibody (4D10) 99/526: Anti-PT S23 subunit Monoclonal Antibody (11E6) 99/528: Anti-PT S23 subunit Monoclonal Antibody (10C9) 99/530: Anti-PT S23 subunit Monoclonal Antibody (10B5) 99/532: Anti-PT S23 subunit Monoclonal Antibody (G9A) 99/534: Anti-PT S23 subunit Monoclonal Antibody (3F6) 99/536: Anti-PT S2 subunit Monoclonal Antibody (3A12) 99/538: Anti-PT S2 subunit Monoclonal Antibody (2H3) 99/540: Anti-PT S2 subunit Monoclonal Antibody (9G8) 99/542: Anti-PT S3 subunit Monoclonal Antibody (7E10) 99/544: Anti-PT S3 subunit Monoclonal Antibody (7G11) 99/546Anti-PT S3 subunit Monoclonal Antibody (4G5) >99/548: Anti-PT S3 subunit Monoclonal Antibody (2E12) 99/550: Anti-PT S3 subunit Monoclonal Antibody (6F8) 99/554: Anti-PT S4 subunit Monoclonal Antibody (7F2) 99/556: Anti-PT S4 subunit Monoclonal Antibody (6B3) 99/558: Anti-PT S4 subunit Monoclonal Antibody (6G8) 99/560: Anti-PT S4 subunit Monoclonal Antibody (9F3) 99/562: Anti-PT S4 subunit Monoclonal Antibody (1H2) 99/564: Anti-PT S4 subunit Monoclonal Antibody (9C6) 99/566: Anti-PT S4 subunit Monoclonal Antibody (6D6) 99/568: Anti-PT S5 subunit Monoclonal Antibody (7E3) Anti Filamentous Haemagglutinin Monoclonal Antibody (1C6) 99/572: Anti-Filamentous Haemagglutinin Monoclonal Antibody (2E9) 99/574: Anti Filamentous Haemagglutinin Monoclonal Antibody (12G10) JNIH-11: Bordetella pertussis anti FHA serum (mouse) JNIH-12: Bordetella pertussis PT( LPF) anti serum, (mouse) JNIH-3: Acellular Pertussis Vaccine (1st International Standard) JNIH-4: Bordetella pertussis filamentous haemagglutinin (FHA)15/126: Bordetella pertussis toxin (20µg) (2nd International Standard18/146: Pertussis antiserum (human) panel18/154: Bordetella pertussis, pertactin, PRN