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Immunization is the best way to prevent seasonal epidemics and pandemics of influenza. There are two kinds of influenza vaccines available in the United States: an inactivated vaccine (TIV) and an attenuated vaccine; however, only TIV is approved for immunization of the elderly population. While the aged population has the highest rate of influenza vaccination, the protective efficacy is low as evidenced by elderly individuals having the highest mortality associated with influenza. Recently, we reported that an adjuvant derived from the helminth parasite Onchocerca volvulus , named O. volvulus activation-associated secreted protein-1 ( Ov -ASP-1), can significantly enhance the protective efficacy of an inactivated vaccine (TIV) in young adult mice. In the current study, we examined whether this recombinant Ov -ASP-1 (r Ov -ASP-1) can enhance the efficacy of TIV in aged mice as well. While primary immunization with TIV alone produced only a low level of influenza-specific antibodies (total IgG, IgG1, and IgG2c) in aged mice, the antibody levels were significantly increased after immunization with TIV + r Ov -ASP-1. More importantly, the level of the total IgG in aged mice administered TIV + r Ov -ASP-1 was comparable to that of young adult mice immunized with TIV alone. Co-administration of r Ov -ASP-1 induced a low level of cross-reactive antibody and enhanced the protective efficacy of TIV in aged mice, reflected by significantly increased survival after challenge with a heterologous influenza virus. r Ov -ASP-1 was also superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice, and in conferring protection after challenge. These results demonstrate that r Ov -ASP-1 may serve as a potential adjuvant for influenza vaccine to improve the efficacy of protection in the elderly. [ABSTRACT FROM AUTHOR]

The Onchocerca volvulus activation-associated secreted protein-1 ( Ov -ASP-1) has good adjuvanticity for a variety of antigens and vaccines, probably due to its ability activate antigen-processing cells (APCs). However, the functional domain of Ov -ASP-1 as an adjuvant is not clearly defined. Based on the structural prediction of this protein family, we constructed a 16-kDa recombinant protein of Ov -ASP-1 that contains only the core pathogenesis-related-1 (PR-1) domain (residues 10–153), designated ASPPR. We found that ASPPR exhibits adjuvanticity similar to that of the full-length Ov -ASP-1 (residues 10–220) for various antigens, including ovalbumin (OVA), HBsAg protein antigen, and the HIV peptide 5 (Pep5) antigen, but it is more suitable for vaccine design in ASPPR-antigen fusion proteins, and more stable in PBS than Ov -ASP-1 stored at −70 °C. These results suggest that ASPPR might be the functional region of Ov -ASP-1 as an adjuvant, and therefore could be developed as an adjuvant for human use. [ABSTRACT FROM AUTHOR]

Highlights: [•] rOv-ASP-1 enhances a stronger antibody response to influenza vaccine. [•] rOv-ASP-1 enhances cross-reactive antibody responses to influenza vaccine. [•] rOv-ASP-1 enhances the protection afforded by an inactivated influenza vaccine after challenge with a heterologous influenza virus. [Copyright &y& Elsevier]

Abstract: Alum, the only adjuvant approved for clinical applications, can induce strong humoral (Th2) but weak cellular (Th1) immune responses. It is necessary to develop safe and effective adjuvants capable of inducing both humoral and cellular immune responses. We previously showed that activation-associated protein-1 (ASP-1) derived from Onchocerca volvulus has potent adjuvant activity. In this study, we have further evaluated the adjuvanticity of recombinant ASP-1 using a panel of recombinant proteins or synthetic peptide-based antigens, including ovalbumin (OVA), synthetic HIV peptide (HIV-p), recombinant HIV gp41 (rgp41) and HBV HBsAg, as well as three commercially available inactivated vaccines against haemorrhagic fever with renal syndrome (HFRS), Influenza and Rabies. Our results indicate that ASP-1 induced significantly higher IgG1 (Th2-associated) and IgG2a (Th1-associated) responses than alum adjuvant against OVA antigen, HIV-p, and rgp41. Consistently, it induced similar level of IgG1 responses as alum but higher level of IgG2a and IFN-γ-producing T cell responses than alum adjuvant against HBsAg. Further, ASP-1 improved both IgG1 and IgG2a responses to three commercial inactivated vaccines when used separately or in combination. In conclusion, the recombinant ASP-1, unlike alum adjuvant, is able to induce both Th1 and Th2-associated humoral responses and Th1 cellular responses, suggesting that it can be further developed as a promising adjuvant for subunit-based and inactivated vaccines. [Copyright &y& Elsevier]

Abstract: We studied the adjuvanticity of recombinant Onchocerca volvulus activation associated protein-1 (rOv-ASP-1) for ovalbumin (OVA) in mice. After a single immunization and one boost, rOv-ASP-1 exceeded the efficacy of alum or MPL+TDM adjuvants in terms of end-point total IgG or IgG1 and IgG2a anti-OVA titres. Using the helminth-derived adjuvant, IgG isotype responses to OVA were of a mixed Th1/Th2 profile and spleen cell cytokines exclusively Th1-type. The potent adjuvanticity of rOv-ASP-1 was confirmed in mice vaccinated with a 37-mer peptide from the S protein of SARS-CoV and an HIV-1 gp120-CD4 chimeric polypeptide antigen. Unusually for a helminth product, the rOv-ASP-1 adjuvant augmented not only Th2 but also Th1 responses, the latter property being of potential utility in stimulating anti-viral immune responses. [Copyright &y& Elsevier]