The present invention relates to enhancing, modulating or stimulating the innate immune response to HIV-1 and other viral pathogens and to the modulation and application of immune modulators and peptides for HIV-1 or other pathogen vaccines. The invention provides methods and means to activate an innate response to HIV-1 utilizing or via the HIV capsid protein or peptide, including modulating the binding of cyclophilin A to HIV capsid protein and modulating the ability of HIV to activate the major innate transcription factor IRF3 and interferon. Methods and assays are provided for screening for compounds, agents, or peptides capable of enhancing or activating innate immune response, particularly to HIV-1.