The Journal of Allergy and Clinical Immunology: In Practice
Original ArticleWhole-Cell Pertussis Vaccination and Decreased Risk of IgE-Mediated Food Allergy: A Nested Case-Control Study
Introduction
Allergic diseases are a major cause of morbidity; asthma alone affects more than 235 million individuals worldwide.1 In high-income countries such as Australia, rates of asthma and allergic rhinitis have plateaued over the past 2 decades,2 while a “second wave” of allergic disease has emerged, manifesting primarily as increasing rates of food allergy.3 In the 12 years to 2005, hospitalizations coded as food-related anaphylaxis more than doubled in Australia4 while a study of infants found that 10% had challenge-proven IgE-mediated food allergy.5 High prevalence of food allergy has also been documented in the United Kingdom6 and in the United States.7
Allergic diseases result from immune dysfunction. Infancy is the period of greatest risk for the development of allergic sensitization, partly due to the inherent TH2 bias of the immature immune system.8 It has been postulated that exposure to TH1-trophic microbial stimuli drives maturation of the immune system in the postnatal period,9 and the growing adoption of Western lifestyles has reduced much of this beneficial TH1-trophic exposure, delaying immune maturation and increasing rates of allergic disease.10
In Australia, an abrupt increase in hospitalizations for food allergy11 coincided with the replacement of multivalent vaccines containing whole-cell pertussis (wP) antigens with acellular pertussis (aP) antigens from 1997 to 2000.12 aP vaccines have since been adopted in most high-income countries primarily because of their lesser reactogenicity,13 although wP vaccines remain the predominant vaccine type used for infant pertussis immunization worldwide.14
wP vaccines comprise killed bacteria, whereas aP vaccines comprise purified subunit antigens, and they induce distinct immune responses; wP vaccines induce a TH1/TH17 immune response in infants,15 whereas aP vaccines elicit an initial strong TH2-dominant immune response.16 Qualitative differences in vaccine responses among children who receive wP versus aP vaccines may be detectable for many years after vaccination.15 Because of their intrinsic TH1-trophic properties, we postulate that wP vaccines might protect against allergic diseases by promoting the normal maturation of the infant immune system whereas aP vaccines do not aid in this maturation.
Given the qualitative differences in the immune responses elicited by wP and aP vaccines, and the observed increase in food allergies after the replacement of wP with aP vaccines in Australia, we further hypothesized that wP vaccination in early infancy might protect against the development of food allergies and sought to test this using a retrospective case-control study.
Section snippets
Ethical approval
The study was approved by all relevant human research ethics committees: Western Australia Child and Adolescent Health Services (2015052EP), Women's and Children's Hospital (HREC/15/WCHN/162), Royal Children's Hospital (35230A), and Sydney Children's Hospital Network (HREC/15/SCHN/405). A waiver of consent was granted for this study.
Setting
The case-control study was registered (NCT02490007) and the protocol detailed previously.17 Briefly, cases and their matched controls were Australian children born
Results
We identified 579 children who met the case definition for IgE-mediated food allergy across the 4 jurisdictions, of whom 502 (87%) had documented receipt of a pertussis vaccine in the first 16 weeks of life (Table I). Of these, 24% (119) had allergies reported to more than 1 food (Table II). The most common food allergies were to peanut (52% [261]), tree nuts (28% [138]), and egg (20% [99]). For the sensitivity analysis, 331 cases (66%) had either the SPT wheal diameter or ssIgE at or above the
Discussion
We found evidence that Australian children born in the late 1990s who received 1 or more doses of wP vaccine in early infancy were less likely to develop food allergies than contemporaneous children who received aP vaccines. If corroborated in a prospective clinical trial, this could provide justification for preferentially priming infants with wP rather than aP vaccines to reduce the subsequent risk of food allergy.
Although the exact cause of the rise in allergic diseases is unknown, atopy is
Acknowledgments
We thank Dr R. Nolan and Dr C.P. Sommerville for support of the study at their respective allergy clinic sites.
References (44)
- et al.
Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys
Lancet (London, England)
(2006) - et al.
Trends in hospitalizations for anaphylaxis, angioedema, and urticaria in Australia, 1993-1994 to 2004-2005
J Allergy Clin Immunol
(2007) - et al.
Epidemiology of food allergy
Immunol Allergy Clin North Am
(2018) - et al.
Role of microbial burden in aetiology of allergy and asthma
Lancet (London, England)
(1999) - et al.
Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012
J Allergy Clin Immunol
(2015) - et al.
Comparison of adverse events following immunisation with acellular and whole-cell pertussis vaccines: a systematic review
Vaccine
(2018) Update on food allergy
J Allergy Clin Immunol
(2004)Food allergy: past, present and future
Allergol Int
(2016)- et al.
Cesarean delivery, preterm birth, and risk of food allergy: nationwide Swedish cohort study of more than 1 million children
J Allergy Clin Immunol
(2018) - et al.
Th1 versus Th2 T cell polarization by whole-cell and acellular childhood pertussis vaccines persists upon re-immunization in adolescence and adulthood
Cell Immunol
(2016)
Transiently increased IgE responses in infants and pre-schoolers receiving only acellular diphtheria-pertussis-tetanus (DTaP) vaccines compared to those initially receiving at least one dose of cellular vaccine (DTwP)—immunological curiosity or canary in the mine?
Vaccine
The natural history of food allergy
J Allergy Clin Immunol Pract
The natural history of tree nut allergy
J Allergy Clin Immunol
No association between atopic outcomes and type of pertussis vaccine given in children born on the Isle of Wight 2001-2002
J Allergy Clin Immunol Pract
Varicella vaccine effectiveness over 10 years in Australia: moderate protection from 1-dose program
J Infect
Parental and community acceptance of the benefits and risks associated with meningococcal B vaccines
Vaccine
WAO white book on allergy: update 2013
Food allergy: riding the second wave of the allergy epidemic
Pediatr Allergy Immunol
Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants
J Allergy Clin Immunol
International prevalences of reported food allergies and intolerances: comparisons arising from the European Community Respiratory Health Survey (ECRHS) 1991-1994
Eur J Clin Nutr
Unbalanced neonatal CD4(+) T-cell immunity
Front Immunol
Hay fever, hygiene, and household size
BMJ
Cited by (15)
Infant Whole-Cell Versus Acellular Pertussis Vaccination in 1997 to 1999 and Risk of Childhood Hospitalization for Food-Induced Anaphylaxis: Linked Administrative Databases Cohort Study
2024, Journal of Allergy and Clinical Immunology: In PracticeVaccine Hesitancy: Drivers and How the Allergy Community Can Help
2021, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :The aP vaccine is associated with a Th2-like immune response and it has been suggested that this might predispose to atopic disease.43 Estcourt et al44 recently reported results from a nested case-control study in Australia, which found a lower odds ratio (0.77; 95% confidence interval [95% CI] 0.62-0.95) in infants receiving a first dose of wP (rather than aP) among cases of food allergy. An adaptive randomized controlled trial of a mixed wP/aP vaccine schedule is now under way to further investigate this.45
Nanoparticles and trained immunity: Glimpse into the future
2021, Advanced Drug Delivery ReviewsA Potential Role for Epigenetically Mediated Trained Immunity in Food Allergy
2020, iScienceCitation Excerpt :More recent RCTs have come to the same conclusion, showing that neonatal BCG vaccination had no effect on allergic sensitization or asthma/wheeze (Thostesen et al., 2017a, 2017b). Another existing vaccine that may influence allergy is the whole-cell killed pertussis (wP) vaccine (Estcourt et al., 2019). In a recently published Australian case-control study, infants who received the first dose of wP were 23% less likely to be diagnosed with food allergy (Estcourt et al., 2019).
The Law of Unintended Consequences in Pertussis Vaccination: An Ounce of Prevention, a Pound of Cure, and … Food Allergy?
2020, Journal of Allergy and Clinical Immunology: In Practice
This research was funded by the National Health and Medical Research Council (NHMRC) of Australia (https://www.nhmrc.gov.au/funding). The NHMRC Project Grant (grant no. APP1069772) was awarded to T.L.S., D.E.C., M.S.G., P.R., K.J.A., H.E.Q., C.S.W., N.J.W., P.B.M., and P.G.H. T.L.S. is supported by an NHMRC Career Development Fellowship (GNT1111657). The funder of the study approved the study design, but had no role in the collection, analysis, and interpretation of data, or in the writing of the report or the decision to submit it for publication.
Conflicts of interest: P. Richmond reports a previous grant from GlaxoSmithKline and has served on advisory panels for GlaxoSmithKline and Sanofi with no remuneration. K. J. Allen is currently a member of the Australian Parliament, but all work for this article was undertaken before April 12, 2019, by which time she had resigned from all paid and honorary appointments listed. No other authors report any relevant conflicts of interest.