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The use of an adjuvant in vaccination is thought to be effective for enhancing immune responses to various pathogens. We genetically constructed a live attenuated simian human immunodeficiency virus (SHIV) to express the adjuvant molecule Ag85B (SHIV-Ag85B). SHIV-Ag85B could not be detected 4 weeks after injection in cynomolgus macaques, and strong SHIV-specific T cell responses were induced in these macaques. When the macaques in which SHIV-Ag85B had become undetectable were challenged with pathogenic SHIV89.6P at 37 weeks after SHIV-Ag85B had become undetectable, SHIV89.6P was not detected after the challenge. Eradication of SHIV89.6P was confirmed by adoptive transfer experiments and CD8-depletion studies. The SHIV-Ag85B-inoculated macaques showed enhancement of Gag-specific monofunctional and polyfunctional CD8+ T cells in the acute phase of the pathogenic SHIV challenge. The results suggest that SHIV-Ag85B elicited strong sterile immune responses against pathogenic SHIV and that it may lead to the development of a vaccine for AIDS virus infection. [ABSTRACT FROM AUTHOR]

The development of a universal influenza vaccine that can provide a robust and long-lasting protection against a broader range of influenza virus strains is a global public health priority. One approach to improve vaccine efficacy is to use an adjuvant to boost immune responses to the target antigens; nevertheless, the role of adjuvants in the context of influenza vaccines is not fully understood. We have previously developed the K3-schizophyllan (SPG) adjuvant, which is composed of nanoparticulated oligodeoxynucleotides K3, a TLR9 agonist, with SPG, a non-agonistic β-glucan ligand of Dectin-1. In this study, K3-SPG given with conventional influenza hemagglutinin (HA) split vaccine (K3-SPG HA) conferred protection against antigenically mismatched heterologous virus challenge. While K3-SPG HA elicited robust cross-reactive HA-specific IgG2c and CD8 T-cell responses, CD8 T-cell depletion had no impact on this cross-protection. In contrast, K3-SPG HA was not able to confer protection against heterologous virus challenge in FcRγ-deficient mice. Our results indicated that FcγR-mediated antibody responses induced by the HA antigen and K3-SPG adjuvant were important for potent protection against antigenically mismatched influenza virus infection. Thus, we demonstrated that the K3-SPG-adjuvanted vaccine strategy broadens protective immunity against influenza and provides a basis for the development of next-generation influenza vaccines. [ABSTRACT FROM AUTHOR]