Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses

Aluminum salts gels (alum) are tlr-independent adjuvants and have been used to boost antibody responses in alum-based vaccines such as diphtheria,pertussis,and tetanus toxoid (dpt) triple vaccine. however,the pro-th2 activity of alum-based vaccine formulations has not been fully appreciated. here we found that alum-based tetanus toxoid (tt) vaccine was biased toward a th-2 profile as shown by tt-induced airway eosinophilic inflammation,type 2 cytokine production,and high levels of ige anaphylactic antibodies. the adsorption into alum of prototypic tlr4 agonists such as lipopolysaccharides (lps) derived from escherichia coli consistently dampened tt-induced th2 activities without inducing ifnγ or th1-like responses in the lung. conversely,adsorption of monophosphoryl lipid a (mpla) extracted from salmonella minnesota,which is a tir-domain-containing adapter-inducing interferon-β-(trif-) biased tlr4 agonist,was less effective in decreasing th-2 responses. importantly,in a situation with antigenic competition (ova plus tt),tt-specific igg1 or igg2a was decreased compared with tt sensitization. notably,lps increased the production of igg1 and igg2a tt-specific antibodies. in conclusion,the addition of lps induces a more robust igg1 and igg2a tt-specific antibody production and concomitantly decreases th2-cellular and humoral responses,indicating a potential use of alum/tlr-based vaccines. © 2015 juliana bortolatto et al.