Intranasal immunization with CpG oligodeoxynucleotides as an adjuvant dramatically increases IgA and protection against herpes simplex virus-2 in thegenital tract

Development of vaccines capable of preventing the transmission or limiting the severity of sexually transmitted viruses, such as HSV and HIV, mill lik ely be dependent on the induction of potent long-lasting mucosal immune res ponses in the genital tract. Recently, synthetic oligodeoxynucleotides (ODN ) containing immunostimulatory CpG motifs were shown to serve as potent adj uvants for the induction of mucosal immune responses. Here, we show that in tranasal immunization with CpG ODN, plus recombinant glycoprotein B (rgB) o f HSV-1, results in significantly elevated levels of specific anti-gB IgA A bs in vaginal washes that remained high throughout the estrous cycle. Addit ionally, dramatically elevated numbers of specific IgA Ab-secreting cells w ere present and persisted in the genital tract in response to intravaginal (IVAG) HSV-2 challenge. HSV-2-specific CTL were observed at moderate levels in the spleens of CpG or non-CpG ODN-immunized mice. In contrast, strong C TL responses were observed locally in the genital tissues of both groups fo llowing IVAG HSV-2 challenge. Interestingly, mice immunized intranasally wi th rgB plus CpG ODN, but not non-CpG ODN, were significantly protected foll owing IVAG HSV-2 challenge. Measurement of virus in protected CpG-immunized mice revealed a log lower level of replication within the first few days a fter infection. In conclusion, these results indicate that intranasal immun ization with CpG ODN plus protein mediates immunity in the female genital t ract capable of protecting against a sexually transmitted pathogen.