It has already been shown that tetanus toxoid (TTd) hyper-immunization is a suitable experimental method for creating the animal model of antiphospholipid syndrome (APS) in BALB/c mice. The severity of APS pathology in BALB/c mice mainly correlates to the affinity of anti-β(2) glycoprotein I (β(2)GPI) antibodies. In this study we have investigated reproductive pathology induced in C57BL/6 mice by TTd hyper-immunization using a combination of different pretreatments (complete Freund's adjuvant or glycerol) and adjuvants (alhydrogel or glycerol). A decrease in fecundity was recorded in only C57BL/6 mice immunized with alhydrogel adjuvant, irrespective of the kind of applied pretreatment; it was associated with an increase in abundance of low affinity anti-β(2)GPI IgG antibodies and Th1 prevalence.

BackgroundIn a quest for a needle-free vaccine administration strategy, we evaluated the ocular conjunctiva as an alternative mucosal immunization route by profiling and comparing the local and systemic immune responses to the subcutaneous or conjunctival administration of tetanus toxoid (TTd), a model antigen.Materials and methodsBALB/c and C57BL/6 mice were immunized either subcutaneously with TTd alone or via the conjunctiva with TTd alone, TTd mixed with 2% glycerol or TTd with merthiolate-inactivated whole-cell B. pertussis (wBP) as adjuvants. Mice were immunized on days 0, 7 and 14 via both routes, and an evaluation of the local and systemic immune responses was performed two weeks after the last immunization. Four weeks after the last immunization, the mice were challenged with a lethal dose (2 × LD50) of tetanus toxin.ResultsThe conjunctival application of TTd in BALB/c mice induced TTd-specific secretory IgA production and skewed the TTd-specific immune response toward a Th1/Th17 profile, as determined by the stimulation of IFNγ and IL-17A secretion and/or the concurrent pronounced reduction of IL-4 secretion, irrespective of the adjuvant. In conjunctivaly immunized C57BL/6 mice, only TTd administered with wBP promoted the establishment of a mixed Th1/Th17 TTd-specific immune response, whereas TTd alone or TTd in conjunction with glycerol initiated a dominant Th1 response against TTd. Immunization via the conjunctiva with TTd plus wBP adjuvant resulted in a 33% survival rate of challenged mice compared to a 0% survival rate in non-immunized animals (p<0.05).ConclusionConjunctival immunization with TTd alone or with various adjuvants induced TTd-specific local and systemic immune responses, predominantly of the Th1 type. The strongest immune responses developed in mice that received TTd together with wBP, which implies that this alternative route might tailor the immune response to fight intracellular bacteria or viruses more effectively.

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Natural antibodies (NAbs) are present in circulation even before the exposure to antigen and they exert various biological functions. They are polyreactive and mainly represented by immunoglobulin M (IgM), which is the first antibody produced in an ongoing immune response to infection and/or immunization. IgM is always secreted as a polymer with predominant pentameric structure, although other polymeric forms such as hexamer can be also formed. The biological functions of hexameric IgM are still not known and it is proposed that its existence as a NAb could be deleterious. However, the nature of IgM hexamers has not been investigated yet. In this paper, we have tested the expression of natural idiotope and antigenic specificities of pentameric and hexameric IgM polymers originating from sera of patients with Waldenström's macroglobulinemia, as well as patients suffering from recurrent urinary bacterial infections. We demonstrate that although pentameric IgM polymers can exist as natural and immune antibodies, IgM hexamers are exclusively immune and do not exist as NAbs.