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Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children., Competing Interests: RJH and LEK served on Health Canada’s Scientific Advisory Committee on Health Products Containing Cannabis whose views are not reflected in this manuscript. RJH received a grant from the Jim Pattison Children’s Hospital Foundation for a study on medical cannabis in childhood refractory epilepsy and was Co-Chair, Health Canada Scientific Advisory Committee on Health Products Containing Cannabis (an unpaid position). EL received speaking fees from Spectrum Therapeutics and holds leadership positions in the following groups: Jamaican Medical Cannabis Corporation (unpaid position), Medical Cannabis Clinicians Society (UK), Canadian Collaborative for Childhood Cannabinoid Therapeutics, MedCan Support and Canadian Patient Advocacy & Support Services. CM-H is the controlling shareholder of a small publicly traded company that made an incremental $1.7M investment in a biotechnology company involved in medical research related to minor cannabinoids. JA has participated in an advisory board for Zyus Life Science. REB is a member of the Advisory Council, Drug-Free Kids Canada, and was Co-Chair of the Cannabis Project Advisory Group, Canadian Paediatric Society (both unpaid positions). SC holds a leadership position on the Network of Networks (N2) Board of Directors. AG reports that this article was researched and written prior to her employment at Health Canada and any views, opinions, and recommendations expressed within are those of the authors and do not reflect the position of Health Canada and/or the Government of Canada. JJ received grants from NSERC, CIHR, AMA Pediatrics, and Alberta Children’s Hospital Foundation, consulting fees from EISAI, UCB, and PENDOPHARM, payment/honoraria from EISAI, UCB, PENDOPHARM, and SUNOVION, and travel reimbursement from Neurocrine. JJ also holds leadership positions in the American Epilepsy Society, the Canadian League Against Epilepsy, and Hope for Hypothalamic Hamartomas. MJR is a member of the Paediatrics & Child Health editorial board. Another editor was responsible for overseeing the peer review of this manuscript. AS is the founder of Shackelford Pharma., an emerging medical cannabis company. There is also a provisional patent application filed, but not yet issued, on behalf of Shackelford Pharma, Inc. RV was director of the Department of Pediatric Pharmacy, Children’s Hospital of Eastern Ontario when this manuscript was written and submitted for publication but is now Vice President of Pharmacy Affairs for BCE Pharma. He has received consulting fees from Harvest Medicine Clinic and recently concluded an 8-year term as a Director of the International Pharmaceutical Federation Foundation. LEK holds a Board of Directors position at the Canadian Consortium for the Investigation of Cannabinoids and holds funding from the Canadian Institutes of Health Research, the Canadian Cancer Society, and the SickKids Foundation for C4T. She holds a Mitacs Accelerate grant for a separate project in partnership with Canopy Growth. There are no other disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Paediatric Society.)

Whooping cough is a respiratory illness most severe in infants and young children. While the introduction of whole-cell (wP) and acellular pertussis (aP) vaccines has greatly reduced the burden of the disease, pertussis remains a problem in neonates and adolescents. New vaccines are needed that can provide early life and long-lasting protection of infants. Vaccination at an early age, however, is problematic due to the interference with maternally derived antibodies (MatAbs) and the bias towards Th2-type responses following vaccination. Here we report the development of a novel vaccine formulation against pertussis that is highly protective in the presence of MatAbs. We co-formulated pertussis toxoid (PTd) and filamentous hemagglutinin (FHA) with cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN), cationic innate defense regulator (IDR) peptide and polyphosphazene (PP) into microparticle and soluble vaccine formulations and tested them in murine and porcine models in the presence and absence of passive immunity. Vaccines composed of the new adjuvant formulations induced an earlier onset of immunity, higher anti-pertussis IgG2a and IgA titers, and a balanced Th1/Th2-type responses when compared to immunization with Quadracel(®), one of the commercially available vaccines for pertussis. Most importantly, the vaccines offered protection against challenge infection in the presence of passively transferred MatAbs., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Whooping cough caused by infection with Bordetella pertussis, is a serious illness in infants and young children. Mortality due to whooping cough is being reported in infants too young to be immunized as well as those who have not completed their series of vaccinations. One of the major factors that interferes with successful active immunization in early life is the presence of maternal antibodies (MatAbs). Using the mouse and pig models, we evaluated the effect of maternal antibodies on active immunization with pertussis toxoid (PTd) and explored strategies to overcome this interference. Our results indicate that passively transferred maternal antibodies interfered with active immunization using pertussis toxoid. The level of passively transferred antibodies directly correlated with the level of interference observed. However, this interference could be overcome by using a second booster immunization or by co-formulating the toxoid with novel adjuvants. These results support the need for novel vaccine formulations that are optimized for the neonate and that can be used not only to modulate the inherently biased neonatal immune system but also to prime the response in the presence of passively transferred maternal antibodies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A balanced or Th-1 type immune response is required for effective clearance of many pathogens such as Bordetella pertussis, the causative agent of whooping cough. Since current acellular pertussis vaccines induce limited Th-1 type immune responses, novel vaccine formulations are needed to induce protective immunity in the infant in the earliest stages of life. Here, we developed a novel vaccine platform consisting of genetically detoxified pertussis toxoid (PTd) with multiple adjuvant components including CpG oligodeoxynucleotides, polyphosphazenes, and cationic innate defence regulator peptides. Co-formulation with these immunomodulators increased the serum IgG2a and IgG1 antibody titres in adult mice when compared to immunization with each of the selected adjuvants or immunization with PTd antigen alone. When used in combination, these adjuvants were able to induce a superior IgG2a response in both adult and neonatal mice, when compared to antigen alone or commercial vaccines. The increased response observed when using this adjuvant formulation was also initiated earlier and, moreover, was maintained over a period of greater than 22 months. The adjuvant platform also showed an ability to induce an immune response in a greater number of mice as compared to antigen alone. This suggests that this uniquely adjuvanted vaccine induces a stronger and more balanced immune response with an earlier onset of this response than vaccination with PTd antigen alone., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Adjuvants are important components of vaccine formulations. Their functions include the delivery of antigen, recruitment of specific immune cells to the site of immunization, activation of these cells to create an inflammatory microenvironment, and maturation of antigen-presenting cells for enhancement of antigen-uptake and -presentation in secondary lymphoid tissues. Adjuvants include a large family of molecules and substances, many of which were developed empirically and without knowledge of their specific mechanisms of action. The discovery of pattern recognition receptors including Toll-like-, nucleotide-binding oligomerization domain (NOD)- and mannose-receptors, has significantly advanced the field of adjuvant research. It is now clear that effective adjuvants link innate and adaptive immunity by signaling through a combination of pathogen recognition receptors (PRRs). Research in our lab is focused towards the development of novel adjuvants and immunomodulators that can be used to improve neonatal vaccines for humans and animals. Using a neonatal pig model for pertussis, we are currently analyzing the effectiveness of host defence peptides (HDPs), bacterial DNA and polyphosphazenes as vaccine adjuvants.