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Canadian Journal of Public Health

, Volume 108, Issue 1, pp e62–e70 | Cite as

A systematic review and meta-analysis for the adverse effects, immunogenicity and efficacy of Lyme disease vaccines: Guiding novel vaccine development

  • Alaa Badawi
  • Maria Shering
  • Shusmita Rahman
  • L. Robbin Lindsay
Systematic Review

Abstract

BACKGROUND: Lyme borreliosis (LB) is the most prevalent arthropod-borne infectious disease in North America. Currently, no vaccine is available to prevent LB in humans, although monovalent and multivalent vaccines have been developed in the past.

OBJECTIVE: The aim of the current study is to conduct a systematic review and meta-analysis to evaluate and compare the findings from these two classes of vaccines for their reactogenicity, immunogenicity and efficacy, in the hope this may assist in the development of future vaccines.

METHODS: A search strategy was developed for online databases (PubMed, Ovid MEDLINE, and Embase). Search terms used were “vaccine/vaccination”, “Lyme disease/Borreliosis”, “clinical trial(s)” and “efficacy”. Only seven clinical trials were included to compare the results of the monovalent vaccines to those of the multivalent one. Meta-analyses were conducted to evaluate the reactogenicity and immunogenicity of the two vaccine classes. Odds ratio (OR) for LB (and 95% confidence intervals; 95% CI) were calculated for the efficacy of the monovalent vaccine from three different clinical trials at different dose schedules.

RESULTS: Incidence of redness (local adverse effect) and fever (systemic side effect) were, respectively, 6.8- and 2.9-fold significantly lower (p <0.05) in individuals who received multivalent vaccines compared to those receiving the monovalent one. Incidences of all other local and systemic adverse effects were non-significantly lower in the multivalent vaccine compared to the monovalent vaccines. Seroprotection was comparable among individuals who received the two vaccine classes at the 30 µg dose level. Efficacy in the prevention of LB was only evaluated for the monovalent vaccines. OR of LB ranged from 0.49 (95% CI: 0.14–0.70; p < 0.005, vs. placebo) to 0.31 (95% CI: 0.26–0.63; p < 0.005) for the initial and final doses respectively, with an overall OR of 0.4 (95% CI: 0.26–0.63, p < 0.001).

CONCLUSION: The current study further validates that the monovalent and multivalent LB vaccines result in mild local side effects and self-limiting systemic adverse effects, with the multivalent vaccine slightly more tolerable than the monovalent one. Both vaccine classes were similarly highly immunogenic. A new vaccine with high safety standards, better efficacy, low cost, and public acceptance is yet to be developed. Meanwhile, personal protection limiting exposure to ticks is recommended.

Key Words

Lyme disease vaccine clinical trial efficacy systematic review 

Résumé

CONTEXTE: La borréliose de Lyme (BL) est la plus prévalente des maladies infectieuses transmises par les arthropodes en Amérique du Nord. Il n’existe actuellement aucun vaccin pour prévenir la BL chez les humains, mais deux vaccins monovalents et un vaccin multivalent ont été mis au point par le passé.

OBJECTIF: Notre étude vise à mener une revue systématique et des méta-analyses pour évaluer et comparer les constatations sur la réactogénicité, l’immunogénicité et l’efficacité potentielle de ces deux classes de vaccins, dans l’espoir que cela aidera à mettre au point de futurs vaccins.

MÉTHODE: Nous avons élaboré une stratégie de consultation de bases de données en ligne (PubMed, Ovid MEDLINE et Embase). Les termes de recherche utilisés ont été ªvaccine/vaccination« (vaccin/vaccination), ªLyme disease/Borreliosis« (maladie de Lyme/borréliose), ªclinical trial (s)« (essai(s) clinique(s)) et ªefficacy« (efficacité potentielle). Nous n’avons inclus que sept essais cliniques pour comparer les résultats des vaccins monovalents à ceux du vaccin multivalent. Nous avons mené des méta-analyses pour évaluer la réactogénicité et l’immunogénicité des deux classes de vaccins. Des rapports de cotes (RC) pour la BL (et des intervalles de confiance de 95%; IC de 95%) ont été calculés pour déterminer l’efficacité potentielle des vaccins monovalents administrés durant trois essais cliniques menés selon des schémas posologiques différents.

RÉSULTATS: L’incidence de rougeurs (un effet indésirable local) et de fièvre (un effet indésirable général) a été, respectivement, de 6,8 et de 2,9 fois significativement inférieure (p < 0,05) chez les sujets ayant reçu le vaccin multivalent que chez ceux ayant reçu les vaccins monovalents. Les incidences de tous les autres effets indésirables locaux et généraux ont été non significativement inférieures pour le vaccin multivalent que pour les vaccins monovalents. La séroprotection était comparable chez les sujets ayant reçu les deux classes de vaccins en doses de 30 µig. L’efficacité potentielle des vaccins pour prévenir la BL n’a été évaluée que pour les vaccins monovalents. Le RC de la BL variait entre 0,49 (IC de 95%: 0,14–0,70; p < 0,005, contre un placebo) et 0,31 (IC de 95%: 0,26–0,63; p < 0,005) pour les doses initiale et finale, respectivement, avec un RC global de 0,4 (IC de 95%: 0,26–0,63, p < 0,001).

CONCLUSION: L’étude actuelle confirme que les vaccins monovalents et multivalent contre la BL entraînent de légers effets secondaires locaux et des effets indésirables généraux spontanément résolutifs, et que le vaccin multivalent est légèrement mieux toléré que les vaccins monovalents. Les deux classes de vaccins ont la même immunogénicité élevée. Un nouveau vaccin avec des normes de sécurité élevées, une efficacité potentielle accrue, un prix abordable et une bonne acceptation par le public n’est pas encore au point. Entre-temps, il est recommandé de prendre des mesures de protection individuelles pour limiter l’exposition aux tiques.

Mots Clés

maladie de Lyme vaccin essai clinique efficacité potentielle revue systématique 

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Copyright information

© The Canadian Public Health Association 2017

Authors and Affiliations

  • Alaa Badawi
    • 1
  • Maria Shering
    • 2
  • Shusmita Rahman
    • 3
  • L. Robbin Lindsay
    • 4
  1. 1.Public Health Risk Science Division, National Microbiology LaboratoryPublic Health Agency of CanadaTorontoCanada
  2. 2.Faculty of Arts and ScienceUniversity of TorontoTorontoCanada
  3. 3.Dalla Lana School of Public HealthUniversity of TorontoTorontoCanada
  4. 4.National Microbiology LaboratoryPublic Health Agency of CanadaWinnipegCanada

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