We recently developed a novel disease model for pertussis in neonatal pigs.6 Using this model we are currently developing novel vaccine formulations against pertussis, also called whooping cough. Pertussis
is an important disease of infants and young children, causing more than 50 million cases and about 300,000 deaths every year.7 Current vaccines are based on recombinant proteins (acellular vaccine) or inactivated bacteria (whole cell vaccines), and
require multiple immunizations between 2–60 months of age. While this is possible in developed countries, access to multiple
immunizations is limited in developing countries resulting in lower vaccine coverage and less effective protection in many
regions of the world. Funded by the Bill & Melinda Gates Foundation, the Krembil Foundation, and the Canadian Institutes of
Health Research, our project aims at developing a variety of immunomodulators that link innate and acquired immunity and therefore
can provide more effective immune protection in the neonate after fewer immunizations.
Innate Immune Stimulators: CpG DNA
Innate immune stimulators function as adjuvants that can enhance both innate and acquired immunity. The most often used stimulator
of the innate immune system is bacterial DNA or synthetic DNA containing CpG motifs (CpG DNA). CpG DNA activates the immune
system by signaling via toll like receptor 9, which typically results in activation of both innate and acquired immunity.
Treatment with CpG oligonucleotides (ODNs) has been successfully used in a variety of experimental infectious and non-infectious
diseases and clinical studies are in various stages to evaluate CpG ODN therapy against infectious disease, cancer, asthma,
and allergy.8–11 As an adjuvant, CpG ODNs promote predominantly Th1-type immune responses, a quality needed for optimal protection against
intracellular pathogens. Because of the Th2 bias in neonates, however, CpG ODN also represent potential adjuvants for balancing
the immune response in the neonate or skewing it toward a Th1 response, which is needed for a number of diseases including
pertussis.12,13 In this regard, neonatal mice immunized with HBsAg in the presence of CpG developed a predominantly Th1-type immune response,
while immunization with only HBsAg alone induced a Th2-type response.9
Contradicting results have been obtained from in vitro stimulation studies with CpG using neonatal peripheral blood mononuclear cells or dendritic cells. Some studies demonstrated
that stimulation with CpG DNA could elicit Th1 responses in the neonate,
high levels of IgM 16 upregulation of co-stimulatory markers on dendritic cells, and proliferation of cord blood B cells.
Other studies, however, showed that innate responses in the neonate including the production of IFN-α by plasmacytoid dendritic
cells were impaired and Th-2 responses to allergens were increased following addition of CpG DNA to house dust mite allergens.14–19 Despite the controversy, encouraging results have been obtained in our own laboratory, which have confirmed that CpG DNA
is highly active in cord blood cells and can induce similar levels of interferons when compared to adults (Gong, et al.,unpublished
results). However, more research is necessary to fully evaluate the potential of CpG DNA for the use in neonates.