Pesquisa | SciELO

Developing an effective vaccine entails: 1) proper antigenic presentation to the immune system, inducing a response of adequate intensity 2) a long duration for said response 3) the ability to steer this response towards the immune system pattern most suited for the elimination of the pathogen. Among the current crop of adjuvants, only aluminum-based gels and some oil emulsions are compliant with established regulatory and safety requirements and, not surprisingly, have received extensive use. The present work describes the development of a technological framework for the inclusion of virus-like particles (VLP) as adjuvants in vaccine preparations, allowing the induction of a functional immune response in humans that achieves seroconversion and protective antibody levels without the need for additional adjuvants. This technological framework comprises both the production and formulation of antigens as virus-like particles and the use of these VLP as adjuvants for soluble antigens, obtaining high levels of induction of the Th1 cell response which, in combination with the humoral response, have been shown to confer a fully functional immunoprotective status in animal models. Some of the novel aspects of the present work are the development of a common methodology for the obtention and formulation of different VLP; the demonstration that VLP-containing formulations are able to bias response towards a Th1 pattern; the finding that VLP can be used as adjuvants stimulating a fully functional response in humans to soluble antigens; the safety of VLP-adjuvanted formulations and, lastly, the induction of a functional, protective response in animal models and humans.

Humoral and cellular immune responses are currently induced against hepatitis C virus (HCV) core following vaccination with core-encoding plasmids. However, the anti-core antibody response is frequently weak or transient. In this paper, we evaluated the effect of different additives and DNA-protein combinations on the anti-core antibody response. BALB/c mice were intramuscularly injected with an expression plasmid (pIDKCo), encoding a C-terminal truncated variant of the HCV core protein, alone or combined with CaCl2, PEG 6000, Freund's adjuvant, sonicated calf thymus DNA and a recombinant core protein (Co.120). Mixture of pIDKCo with PEG 6000 and Freund's adjuvant accelerated the development of the anti-core Ab response. Combination with PEG 6000 also induced a bias to IgG2a subclass predominance among anti-core antibodies. The kinetics, IgG2a/IgG1 ratio and epitope specificity of the anti-core antibody response elicited by Co.120 alone or combined with pIDKCo was different regarding that induced by the pIDKCo alone. Our data indicate that the antibody response induced following DNA immunization can be modified by formulation strategies.

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