Explore the vast range of titles available.

Seasonal influenza epidemics represent a substantial public health burden, causing significant morbidity and mortality. Influenza in humans can be caused by influenza type A and type B viruses, and although influenza A is responsible for the majority of seasonal influenza infections, influenza B disease is common in children and young adults, and causes seasonal epidemics every 2–4 years. Influenza strains circulating during a seasonal epidemic may be influenza type A strains A/H1N1 and A/H3N2, strains of influenza B lineages B/Victoria and B/Yamagata, or any combination of these. The morbidity and mortality burden of influenza infections means that public health agencies worldwide recommend vaccination to try and protect against seasonal epidemics. The World Health Organization (WHO) and, in the United States of America (USA), the Food and Drug Administration (FDA), recommend trivalent seasonal influenza vaccines containing the two main influenza type A strains and, due to its lesser but still important prevalence, one influenza type B strain. There is little or no cross-reactive protection between the influenza B lineages: this means that good protection against the circulating virus relies on correctly predicting the prevalent influenza B lineage in any season. This has proved to be reliant on chance, and little or no protection has been provided in the USA by the trivalent vaccines against the circulating influenza B virus in 5 of the 10 seasons between 2001 and 2010. There is, therefore, a clear need for a quadrivalent influenza vaccine, containing influenza A/H1N1, A/H3N2, and B/Victoria and B/Yamagata lineage strains, to improve protection against influenza B virus and reduce the morbidity of influenza B infection.

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.

The 1918 virus spread rapidly around the world and was associated with mortality measured in the thousands per 100,000 population. Dr. Robert Belshe describes what the 1918 virus teaches us about avian H5N1 influenza. The completion of the genetic sequencing of the 1918 influenza A virus by Taubenberger et al. 1 and the subsequent recovery of the virus by Tumpey et al. 2 using reverse genetic techniques are spectacular achievements of contemporary molecular biology and provide important insights into the origin of pandemic influenza. The three pandemic viruses that emerged in the 20th century — the 1918 (“Spanish influenza”) H1N1 virus, the 1957 (“Asian influenza”) H2N2 virus, and the 1968 (“Hong Kong influenza”) H3N2 virus — all spread rapidly around the world, but only the 1918 virus was associated with mortality measured in the thousands per . . .

An intranasally administered influenza vaccine may be useful in efforts toward universal vaccination of children less than 5 years of age. In this trial involving 8352 young children, the attack rate for symptomatic influenza was 5% with the live attenuated vaccine, as compared with 10% with the inactivated influenza vaccine administered intramuscularly. However, with the live vaccine, as compared with the inactivated influenza vaccine, there was a higher rate of hospitalization for any cause among children younger than 12 months of age. In this trial involving 8352 young children, the attack rate for symptomatic influenza was 5% with the live attenuated vaccine, as compared with 10% with the inactivated influenza vaccine. However, with the live vaccine, there was a higher rate of hospitalization for any cause among children younger than 12 months of age. Hospitalization rates for culture-confirmed influenza among young children are similar to those among the elderly, and outpatient visits for confirmed influenza are more frequent among infants and young children than in any other age group. 1 For these reasons, U.S. advisory bodies have recently recommended the routine vaccination of all children 6 to 59 months of age with the licensed trivalent inactivated influenza vaccine. 2 The implementation of this recommendation will be challenging because of the limited supplies of inactivated vaccine during many influenza seasons, 3 – 5 the modest efficacy of inactivated vaccine in young children, 6 and the frequent need to administer the . . .

There is no vaccine to prevent herpes simplex virus (HSV) infection. In this trial in 8323 women, a candidate HSV vaccine containing glycoprotein D was found to be ineffective in preventing HSV-2 infection. Both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can cause primary infection of the genital tract, and HSV-1 infection has become an increasingly frequent cause of genital disease. 1 The majority of HSV infections are asymptomatic, and only 10 to 25% of persons with HSV-2 antibodies have recurrent genital disease. 2 , 3 Transmission of HSV from infected women to neonates may lead to severe neurologic disease or death in the newborn. Strategies to control genital herpes infection and disease have mainly focused on antiviral chemotherapy, education, and the use of condoms. The availability of an effective prophylactic vaccine would . . .

The Herpevac Trial evaluated a herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit vaccine to prevent genital herpes. Unexpectedly, the vaccine protected against genital HSV-1 infection but not genital HSV-2 infection. We evaluated sera from 30 women seronegative for HSV-1 and HSV-2 who were immunized with gD2 in the Herpevac Trial. Neutralizing antibody titers to HSV-1 were 3.5-fold higher than those to HSV-2 (P< .001). HSV-2 gC2 and gE2 on the virus blocked neutralization by gD2 antibody, while HSV-1 gC1 and gE1 did not block neutralization by gD2 antibody. The higher neutralizing antibody titers to HSV-1 offer an explanation for the Herpevac results, and shielding neutralizing domains provides a potential mechanism.

After the emergence of pandemic influenza viruses in 1957, 1968, and 2009, existing seasonal viruses were observed to be replaced in the human population by the novel pandemic strains. We have previously hypothesized that the replacement of seasonal strains was mediated, in part, by a population-scale boost in antibodies specific for conserved regions of the hemagglutinin stalk and the viral neuraminidase. Numerous recent studies have shown the role of stalk-specific antibodies in neutralization of influenza viruses; the finding that stalk antibodies can effectively neutralize virus alters the existing dogma that influenza virus neutralization is mediated solely by antibodies that react with the globular head of the viral hemagglutinin. The present study explores the possibility that stalk-specific antibodies were boosted by infection with the 2009 H1N1 pandemic virus and that those antibodies could have contributed to the disappearance of existing seasonal H1N1 influenza virus strains. To study stalk-specific antibodies, we have developed chimeric hemagglutinin constructs that enable the measurement of antibodies that bind the hemagglutinin protein and neutralize virus but do not have hemagglutination inhibition activity. Using these chimeric hemagglutinin reagents, we show that infection with the 2009 pandemic H1N1 virus elicited a boost in titer of virus-neutralizing antibodies directed against the hemagglutinin stalk. In addition, we describe assays that can be used to measure influenza virus-neutralizing antibodies that are not detected in the traditional hemagglutination inhibition assay.

Background. Herpes simplex virus infections type 1 (HSV-1) and type 2 (HSV-2) are common, but the epidemiology of HSV disease is changing. Methods. HSV-seronegative women, aged 18–30 years, who were in the control arm of the HERPEVAC Trial for Women were followed for 20 months for primary HSV infections. Results. Of the 3438 evaluable participants, 183 became infected with HSV: 127 (3.7%) with HSV-1 and 56 (1.6%) with HSV-2. The rate of infection for HSV-1 (2.5 per 100 person-years) was more than twice that for HSV-2 (1.1 per 100 person-years). Most infections (74% of HSV-1 and 63% of HSV-2) occurred without recognized signs or symptoms of herpes disease. The HSV-2 infection rate was 2.6 times higher in non-Hispanic black participants than in Hispanics and 5.5 times higher than in non-Hispanic whites (P < .001), while the HSV-1 infection rate was 1.7 times higher in non-Hispanic whites than non-Hispanic blacks. Younger participants (18–22 years) were more likely to acquire HSV-1 infections and less likely to develop recognized disease than older participants. Overall, 84% of recognized disease cases were genital. No differences were noted in the clinical manifestations of genital HSV-1 vs genital HSV-2 disease. The clinicians' assessment that cases were caused by HSV was good when they assessed cases as clinically confirmed or unlikely (validated in 83% and 100% of cases, respectively). Conclusions. HSV-1 is now more common than HSV-2 as a cause of oral and genital mucosal infections in young women, but there are important age and race differences.

Background. Previously we conducted a double-blind controlled, randomized efficacy field trial of gD-2 HSV vaccine adjuvanted with ASO4 in 8323 women. Subjects had been previously selected to be seronegative for HSV-1 and HSV-2. We found that vaccine was 82% protective against HSV-1 genital disease, but offered no significant protection against HSV-2 genital disease. Methods. To better understand the results of the efficacy study, post-vaccination anti-gD-2 antibody concentrations from all HSV infected subjects and matched uninfected controls were measured. Three models were used to determine whether these responses correlated with protection against HSV infection or disease. Similarly, cellular immune responses from a subset of subjects and matched controls were evaluated for a correlation with HSV protection. Results. Antibodies to gD-2 correlated with protection against HSV-1 infection with higher antibody concentration associated with higher efficacy. Cellular immune responses to gD-2 did not correlate with protection. Conclusions. The protection against HSV-1 infection observed in the Herpevac Trial for Women was associated with antibodies directed against the vaccine. Clinical Trials Registration. NCT00057330.