Targeting CD30 in malignant tissues: challenges in detection and clinical applications.

The CD30 transmembrane receptor from the tumor necrosis factor receptor family is expressed in a distinct, yet diverse set of lymphoproliferative disorders and a small subset of normal activated lymphocytes. Therefore, detection of CD30 expression when performed properly according to the standardized methods facilitates diagnosis of Hodgkin lymphoma, anaplastic large cell lymphoma, and other disorders expressing the receptor. More recently, CD30 has also become an attractive therapeutic target. The preliminary observations indicate that the methods currently used to detect CD30 expression, typically immunohistochemistry performed on formalin-fixed, paraffin-embedded tissues, may be suboptimal in regard to identifying CD30 as a therapeutic target since only a limited number of CD30 receptor molecules per cell may be sufficient to achieve therapeutic effect.

Use of Vaxfectin adjuvant with DNA vaccine encoding the measles virus hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques against measles virus.

A measles virus vaccine for infants under 6 months of age would help control measles. DNA vaccines hold promise, but none has provided full protection from challenge. Codon-optimized plasmid DNAs encoding the measles virus hemagglutinin and fusion glycoproteins were formulated with the cationic lipid-based adjuvant Vaxfectin. In mice, antibody and gamma interferon (IFN-gamma) production were increased by two- to threefold. In macaques, juveniles vaccinated at 0 and 28 days with 500 microg of DNA intradermally or with 1 mg intramuscularly developed sustained neutralizing antibody and H- and F-specific IFN-gamma responses. Infant monkeys developed sustained neutralizing antibody and T cells secreting IFN-gamma and interleukin-4. Twelve to 15 months after vaccination, vaccinated monkeys were protected from an intratracheal challenge: viremia was undetectable by cocultivation and rashes did not appear, while two naïve monkeys developed viremia and rashes. The use of Vaxfectin-formulated DNA is a promising approach to the development of a measles vaccine for young infants.

Vaxfectin-formulated influenza DNA vaccines encoding NP and M2 viral proteins protect mice against lethal viral challenge.

Next generation influenza vaccines containing conserved antigens may enhance immunity against seasonal or pandemic influenza virus strains. Using a plasmid DNA (pDNA)-based vaccine approach, we systematically tested combinations of NP, M1, and M2 antigens derived from consensus sequences for protection against lethal influenza challenge and compared formulations for adjuvanting low pDNA vaccine doses. The highest level of protection at the lowest pDNA doses was provided by Vaxfectin-formulated NP + M2. Vaxfectin adjuvanticity was confirmed with a low dose of HA pDNA. These promising proof-of-concept data support the clinical development of Vaxfectin-formulated pDNA encoding NP + M2 consensus proteins.

Cross-reactive neuraminidase antibodies afford partial protection against H5N1 in mice and are present in unexposed humans.

BACKGROUND: A pandemic H5N1 influenza outbreak would be facilitated by an absence of immunity to the avian-derived virus in the human population. Although this condition is likely in regard to hemagglutinin-mediated immunity, the neuraminidase (NA) of H5N1 viruses (avN1) and of endemic human H1N1 viruses (huN1) are classified in the same serotype. We hypothesized that an immune response to huN1 could mediate cross-protection against H5N1 influenza virus infection. METHODS AND FINDINGS: Mice were immunized against the NA of a contemporary human H1N1 strain by DNA vaccination. They were challenged with recombinant A/Puerto Rico/8/34 (PR8) viruses bearing huN1 (PR8-huN1) or avN1 (PR8-avN1) or with H5N1 virus A/Vietnam/1203/04. Additional naïve mice were injected with sera from vaccinated mice prior to H5N1 challenge. Also, serum specimens from humans were analyzed for reactivity with avN1. Immunization elicited a serum IgG response to huN1 and robust protection against the homologous challenge virus. Immunized mice were partially protected from lethal challenge with H5N1 virus or recombinant PR8-avN1. Sera transferred from immunized mice to naïve animals conferred similar protection against H5N1 mortality. Analysis of human sera showed that antibodies able to inhibit the sialidase activity of avN1 exist in some individuals. CONCLUSIONS: These data reveal that humoral immunity elicited by huN1 can partially protect against H5N1 infection in a mammalian host. Our results suggest that a portion of the human population could have some degree of resistance to H5N1 influenza, with the possibility that this could be induced or enhanced through immunization with seasonal influenza vaccines.