Volume 4 • Issue 1 • 1000175
J Vaccines Vaccin
ISSN:2157-7560 JVV an open access journal
Review Article Open Access
Vaccines & Vaccination
Mukkur and Richmond, J Vaccines Vaccin 2013, 4:1
http://dx.doi.org/10.4172/2157-7560.1000175
Keywords: Bordetella pertussis; Live attenuated vaccines; DNA
vaccines; Biodegradable nanoparticle vaccines; Pertussis
Introduction
Whooping cough (pertussis), a respiratory disease caused by
Bordetella pertussis, accounts for more than 3,00,000 deaths annually
worldwide [1,2] and its incidence has been rising [3]. B. pertussis is a
non-invasive pathogen which localises mainly in the upper respiratory
tract and produces a large array of potential virulence factors, many
of which play signifcant roles in the pathogenesis of pertussis [1,4]. A
killed whole cell pertussis vaccine, generally given in combination with
diphtheria and tetanus toxoids, has been available in many countries
for over 40 years. While its use seems to have controlled pertussis
epidemics, concerns over the reactogenicity, ranging from high fever,
persistent crying, pain and swelling at the site of injection [4,5] led
to the development of the currently marketed acellular pertussis
vaccines (DTaP) which is administered to infants in Australia at 2, 4,
and 6 months with a booster at 4-6 years of age [5]. In other countries
like the USA, children are also vaccinated at 12-18 months of age
[4]. Children under the age of 2 months of age are highly susceptible
to the complications of pertussis infection but are too young to be
immunised. Te concern that young adults (vaccinated during their
childhood) with waning immunity against whooping cough may serve
as a reservoir for the pathogen for infecting infants (and children), has
stimulated interest in the development of an alternative vaccine which
can also be used safely in the adult population [6].
It is generally accepted that the protective efcacy of the acellular
vaccine is short–term, not long-term [7]. Furthermore, given the
frequency of local reactions [5,8], particularly the reported extensive
limb swelling [5] that occured in a children receiving 4
th
booster
vaccinations with DTaP, may raise an alarm, albeit undue, in the
community about the safety of this vaccine. Te alternatives suggested
have been to either to reduce the number of booster immunisation
show ever this would lead to reduced levels of immunity, use vaccines
with reduced antigen content as has been done by introduction of adult
acellular pertussis vaccine formulations, dTpa, for use in adolescents
(http://immunise.health.gov.au), or to fnd a replacement adjuvant,
which, unlike alum, favours the induction of T1 responses that has been
proposed to be responsible for long-term protection against whooping
cough [9]. Unfortunately, no such universally acceptable adjuvant for
use with DTaP approved by the Food and Drugs Administration (FDA)
is available, hence the continued use of the alum-based adjuvants in
pertussis vaccine formulations.
Comparison of the humoral and cellular immune responses of
mice following vaccination with the killed whole cell pertussis vaccine
(WCV:DTPw) versus the DTaP [10] has revealed that although the
DTPw induced lower antibody titres to the pertussis toxin, flamentous
haemagglutinin and pertactin, it was more efective in activating
macrophages and more protective as judged in intracerebral challenge
and bacterial lung clearance experiments than the DTaP [10]. Tese
authors suggested that cell-mediated immunity might play a crucial role
in eliminating bacteria that escape the humoral defence mechanisms.
Tis suggestion is further supported by the fact that B. pertussis can
survive within mammalian cells including macrophages [11,12]. It has
also been suggested that circulating antibodies may play a role in toxin
neutralisation and prevention of bacterial attachment to respiratory
epithelial cells particularly in the early phase of infection [10]. Tere is
now evidence that whole-cell pertussis priming in infancy may be more
efective than DTaP priming on subsequent protection in childhood [13].
*Corresponding author: Trilochan Mukkur, School of Biomedical Sciences, Fa-
culty of Health Sciences, Curtin Health Innovation Research Institute, Curtin Uni-
versity, Bentley, Perth, Western Australia 6102, Australia, Tel: +61892667520; Fax:
+61892662342; E-mail: T.Mukkur@curtin.edu.au
Received December 31, 2012; Accepted January 29, 2013; Published January
31, 2013
Citation: Mukkur T, Richmond P (2013) Alternative Whooping Cough Vaccines: A
Minireview. J Vaccines Vaccin 4: 175. doi:10.4172/2157-7560.1000175
Copyright: © 2013 Mukkur T, et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Alternative Whooping Cough Vaccines: A Minireview
Trilochan Mukkur
1
*and Peter Richmond
2
1
School of Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, Western Australia 6102,
Australia
2
School of Pediatrics and Child Health, University of Western Australia, Princess Margaret Hospital for Children, Perth 6340, Western Australia
Abstract
Bordetella pertussis, the aetiological agent of an acute upper respiratory tract disease of humans, “whooping
cough”, can infect all age groups with adolescents and adults acting as major source of transmission of this pathogen
to infants. This transmission is promoted by the fact that adolescents and adults do not exhibit the characteristic cough,
the infection being either asymptomatic or manifested as a mild but persistent upper respiratory tract infection. It is
established now that both antibodies and cell-mediated immune [CMI] responses are crucial for protection against
whooping cough, the former being important in the early phase of the disease, with the latter being important for
long-term protection. The protection offered by vaccination with the currently-marketed acellular pertussis vaccines
is predominantly due to antibodies against vaccine antigens associated with a Th2-polarised immune response
and has been found to be relatively short-term protection. There is an urgent need to develop alternative vaccines
capable of inducing both protective antibody and CMI responses particularly given the resurgence of this vaccine-
preventable disease in infants and children worldwide. While current strategies are aimed at the development of
recombinant vaccines using an adjuvant that may stimulate both arms of the immune response, no discovery of a
cost-effective and non-toxic adjuvant to improve protection against pertussis has been reported thus far. This review
details the oral presentation on alternative whooping cough vaccines and their future potential delivered at the 2
nd
World Conference on Vaccines and Vaccination organised by the OMICS Publishing Group.