Original Article
Whole-Cell Pertussis Vaccination and Decreased Risk of IgE-Mediated Food Allergy: A Nested Case-Control Study

https://doi.org/10.1016/j.jaip.2019.12.020Get rights and content

Background

Rates of food allergy have increased markedly in Australia and other high- income countries in recent years. On the basis of ecological observations, and the known immunologic characteristics of whole-cell pertussis (wP) compared with acellular pertussis (aP) vaccines, we hypothesized that wP vaccination in infancy protects against the development of food allergy.

Objective

To determine whether infants who receive wP in infancy were less likely to develop IgE-mediated food allergy than those who received aP.

Methods

Retrospective cohort-nested case-control study of Australian children born in the period 1997 to 1999, the period of transition from using wP-containing to aP-containing vaccines. Children diagnosed with IgE-mediated food allergy were individually matched to 10 controls by date of birth, socioeconomic decile, and jurisdiction of birth. The odds ratio of vaccination with wP versus aP among cases and matched controls was calculated using conditional logistic regression.

Results

The odds ratio of receiving the first dose as wP (rather than aP) among cases of food allergy compared with controls was 0.77 (95% CI, 0.62-0.95). The results of secondary analyses (any dose as wP vs aP-only, and wP-only vs aP-only) were broadly similar.

Conclusions

Australian infants who received wP vaccines were less likely to be diagnosed with food allergy in childhood than contemporaneous children who received aP vaccines. If a protective effect is confirmed in a randomized controlled trial, wP or mixed wP and aP vaccination schedules could form part of an effective strategy for combating the rise in food allergies.

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.

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    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.

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