Abstract
Saponin-based adjuvants are widely used to enhance humoral and cellular immune responses towards vaccine antigens, although it is not yet completely known how they mediate their stimulatory effects. The aim of this study was to elucidate the mechanism of action of adjuvant Matrix-M™ without antigen and Alum was used as reference adjuvant. Adjuvant Matrix-M™ is comprised of 40 nm nanoparticles composed of Quillaja saponins, cholesterol and phospholipid. BALB/c mice were subcutaneously injected once with, 3, 12 or 30 µg of Matrix-M™, resulting in recruitment of leukocytes to draining lymph nodes (dLNs) and spleen 48 h post treatment. Flow cytometry analysis identified CD11b+ Gr-1high granulocytes as the cell population increasing most in dLNs and spleen. Additionally, dendritic cells, F4/80int cells, T-, B- and NK-cells were recruited to dLNs and in spleen the number of F4/80int cells, and to some extent, B cells and dendritic cells, increased. Elevated levels of early activation marker CD69 were detected on T-, B- and NK-cells, CD11b+ Gr-1high cells, F4/80int cells and dendritic cells in dLNs. In spleen CD69 was mainly up-regulated on NK cells. B cells and dendritic cells in dLNs and spleen showed an increased expression of the co-stimulatory molecule CD86 and dendritic cells in dLNs expressed elevated levels of MHC class II. The high-dose (30 µg) of Matrix-M™ induced detectable serum levels of IL-6 and MIP-1β 4 h post administration, most likely representing spillover of locally produced cytokines. A lesser increase of IL-6 in serum after administration of 12 µg Matrix-M™ was also observed. In conclusion, early immunostimulatory properties were demonstrated by Matrix-M™ alone, as therapeutic doses resulted in a local transient immune response with recruitment and activation of central immune cells to dLNs. These effects may play a role in enhancing uptake and presentation of vaccine antigens to elicit a competent immune response.
Highlights
Adjuvants are compounds added to vaccine antigens to facilitate and enhance activation of the innate and adaptive immune responses, to improve the immunogenicity and efficacy of vaccines
We show that Matrix-MTM treatment results in a local and transient immune stimulation with recruitment of lymphocytes, macrophages and granulocytes to draining lymph nodes (dLNs) and spleen
These results are in agreement with previous findings with a similar adjuvant where recruitment of lymphocytes to dLNs was reported in sheep after administration of ISCOMATRIXTM [15]
Summary
Adjuvants are compounds added to vaccine antigens to facilitate and enhance activation of the innate and adaptive immune responses, to improve the immunogenicity and efficacy of vaccines. Adjuvants exert their effects through various mechanisms, and the nature and identity of the antigen(s) contributes to the immune response [1]. Basic research on adjuvant properties is central in order to better understand how adjuvants and antigens work in concert, generating a safe and efficacious immune response. Saponins, those obtained from Quillaja saponaria Molina, are known potent adjuvants and Quillaja saponins (QS) have for long been used in animal vaccines. By purification of the QS raw material, distinctive fractions with different characteristics can be defined
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