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Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making a global vaccine an urgent priority given the estimated high incidence of infection around the world. Due to the highly heterogeneous nature of HCV, an effective HCV vaccine which could elicit broadly cross-neutralizing antibodies has represented a major challenge. In this study, we tested for the presence of cross-neutralizing antibodies in human volunteers who were immunized with recombinant glycoproteins gpE1/gpE2 derived from a single HCV strain (HCV1 of genotype 1a). Cross neutralization was tested in Huh-7.5 human hepatoma cell cultures using infectious recombinant HCV (HCVcc) expressing structural proteins of heterologous HCV strains from all known major genotypes, 1–7. Vaccination induced significant neutralizing antibodies against heterologous HCV genotype 1a virus which represents the most common genotype in North America. Of the 16 vaccinees tested, 3 were selected on the basis of strong 1a virus neutralization for testing of broad cross-neutralizing responses. At least 1 vaccinee was shown to elicit broad cross-neutralization against all HCV genotypes. Although observed in only a minority of vaccinees, our results prove the key concept that a vaccine derived from a single strain of HCV can elicit broad cross-neutralizing antibodies against all known major genotypes of HCV and provide considerable encouragement for the further development of a human vaccine against this common, global pathogen. [ABSTRACT FROM AUTHOR]

A phase 2 evaluation of live attenuated parainfluenza type 3 (PIV3)­cold passage mutant 45 (cp45) vaccine was conducted in 380 children 6–18 months old; 226 children (59%) were seronegative for PIV3. Of the 226 seronegative children, 114 received PIV3-cp45 vaccine, and 112 received placebo. No significant difference in the occurrence of adverse events (i.e., runny nose, cough, or temperature ≤38 °C) was noted during the 14 days after vaccination. There was no difference between groups in the occurrence of acute otitis media or serous otitis media. Paired serum samples were available for 109 of the seronegative vaccine recipients and for 110 of the seronegative placebo recipients; 84% of seronegative vaccine recipients developed a ≥4-fold increase in antibody titers. The geometric mean antibody titer after vaccination was 1:25 in the vaccine group and <1:4 in the placebo group. PIV3-cp45 vaccine was safe and immunogenic in seronegative children and should be evaluated for efficacy in a phase 3 field trial. [ABSTRACT FROM AUTHOR]

Abstract: Early in the development of respiratory syncytial virus (RSV) vaccines severe disease occurred in children after receipt of formalin-inactivated RSV vaccine. Continuing efforts to develop an appropriately attenuated and immunogenic live RSV vaccine have given opportunities to assure that live vaccines are safe through surveillance of children after vaccination. In the present study, the rate of RSV-associated upper respiratory tract illness in 388 children was lower in RSV vaccinated children than in controls (14% versus 20% in a 6–24 month old group and 16% versus 25% in infants). Additionally, there was no evidence that vaccination predisposed to more severe lower respiratory tract illness. Thus infection with a series of live attenuated RSV vaccines did not result in enhanced disease upon infection with wild type RSV. The impact of RSV during this surveillance will inform the design of future efficacy studies with RSV vaccines. [Copyright &y& Elsevier]

Background: We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and virus-specific activity of cytotoxic T cells and interferon-γ–producing T cells. Methods: Sixty healthy adults were inoculated intradermally by bifurcated needle with undiluted vaccine (dose, 107.8 plaque-forming units [pfu] per milliliter), a 1:10 dilution (dose, 106.5 pfu per milliliter), or a 1:100 dilution (dose, 105.0 pfu per milliliter); there were 20 subjects in each group. The subjects were monitored with respect to vesicle formation (an indicator of successful vaccination), the viral titer at the time of peak lesion formation, antiviral antibodies, and cellular immune responses. Results: A vaccinia vesicle developed in 19 of the 20 subjects who received undiluted vaccine (95 percent), 14 of the 20 who received the 1:10 dilution (70 percent), and 3 of the 20 who received the 1:100 dilution (15 percent). One month after vaccination, 34 of 36 subjects with vesicles had antibody responses, as compared with only 1 of 24 subjects without clinical evidence of vaccinia virus replication. Vigorous cytotoxic T-cell and interferon-γ responses occurred in 94 percent of subjects with vesicles, and a cytotoxic T-cell response occurred in only one subject without a vesicle. Conclusions: The vaccinia virus vaccine (which was produced in 1982 or earlier) still has substantial potency when administered by a bifurcated needle to previously unvaccinated adults. Diluting the vaccine reduces the rate of successful vaccination. The development of vesicular skin lesions after vaccination correlates with the induction of the antibody and T-cell responses that are considered essential for clearing vaccinia virus infections. (N Engl J Med 2002;346:1275-80.) [ABSTRACT FROM AUTHOR]

Background: To evaluate the potential to increase the supply of smallpox vaccine (vaccinia virus), we compared the response to vaccination with 108.1, 107.2, and 107.0 plaque-forming units (pfu) of vaccinia virus per milliliter. Methods: In this randomized, single-blind, prospective study, 680 adults who had not been previously immunized were inoculated intradermally with undiluted vaccine (mean titer, 108.1 pfu per milliliter), a 1:5 dilution, or a 1:10 dilution of vaccinia virus with use of a bifurcated needle, and the site was covered with a semipermeable dressing. Subjects were monitored for vesicle formation (an indicator of the success of vaccination) and adverse events for 56 days after immunization. Results: Success rates did not differ significantly among the groups and ranged from 97.1 to 99.1 percent after the first vaccination. Both the undiluted and diluted vaccines were reactogenic. In addition to the formation of pustules, common adverse events included the formation of satellite lesions, regional lymphadenopathy, fever, headache, nausea, muscle aches, fatigue, and chills consistent with the presence of an acute viral illness. Generalized and localized rashes, including two cases of erythema multiforme, were also observed. Conclusions: When given by a bifurcated needle, vaccinia virus vaccine can be diluted to a titer as low as 107.0 pfu per milliliter (approximately 10,000 pfu per dose) and induce local viral replication and vesicle formation in more than 97 percent of persons. (N Engl J Med 2002;346:1265-74.) [ABSTRACT FROM AUTHOR]