Suchergebnisse

The emergence of Zika virus in Brazil and its association with microcephaly and Guillain-Barré syndrome led to accelerated vaccine development efforts. Based on prior flavivirus vaccine development programs, knowledge of flavivirus particle structure, definition of E dimers as the key antigenic target, and deep understanding of neutralizing mechanisms, multiple vaccine strategies have advanced to the stage of clinical evaluation with unprecedented speed. These include nucleic acid (DNA and messenger RNA), whole-inactivated virus, live-attenuated or chimeric virus, and protein or viruslike particle vaccines. Within a year from the declaration by the World Health Organization of Zika virus as a Public Health Emergency of International Concern, multiple vaccine candidates entered clinical trials, now totaling 7 products with an additional 40-plus candidate vaccines in preclinical development. The rapid progress in vaccine development demonstrates the capacity of governments, public health organizations, and the scientific community to respond to pandemic threats when sufficient prior knowledge exists, emergency funding is made available, and interagency cooperation is achieved and serves as a paradigm for preparing for future emerging infectious diseases.

AbstractGlobally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV‐1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV‐1 infection. Thus, for the global community to achieve elimination of new paediatric HIV‐1 infections, innovative approaches need to be explored. Immune‐based approaches to prevention of mother‐to‐child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS‐free generation. Immune‐based interventions to prevent MTCT of HIV‐1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof‐of‐concept has been established over the last two decades that passively administered HIV‐1 Env‐specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune‐based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast‐Track 2030 goals to eliminate new paediatric HIV infections.

Ebola viruses represent a class of filoviruses that causes severe hemorrhagic fever with high mortality. Recognized first in 1976 in the Democratic Republic of Congo, outbreaks continue to occur in equatorial Africa. A safe and effective Ebola virus vaccine is needed because of its continued emergence and its potential for use for biodefense. We report the safety and immunogenicity of an Ebola virus vaccine in its first phase I human study. A three-plasmid DNA vaccine encoding the envelope glycoproteins (GP) from the Zaire and Sudan/Gulu species as well as the nucleoprotein was evaluated in a randomized, placebo-controlled, double-blinded, dose escalation study. Healthy adults, ages 18 to 44 years, were randomized to receive three injections of vaccine at 2 mg (n = 5), 4 mg (n = 8), or 8 mg (n = 8) or placebo (n = 6). Immunogenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoprecipitation-Western blotting, intracellular cytokine staining (ICS), and enzyme-linked immunospot assay. The vaccine was well-tolerated, with no significant adverse events or coagulation abnormalities. Specific antibody responses to at least one of the three antigens encoded by the vaccine as assessed by ELISA and CD4+ T-cell GP-specific responses as assessed by ICS were detected in 20/20 vaccinees. CD8+ T-cell GP-specific responses were detected by ICS assay in 6/20 vaccinees. This Ebola virus DNA vaccine was safe and immunogenic in humans. Further assessment of the DNA platform alone and in combination with replication-defective adenoviral vector vaccines, in concert with challenge and immune data from nonhuman primates, will facilitate evaluation and potential licensure of an Ebola virus vaccine under the Animal Rule.

Studies on the burden of human monkeypox in the Democratic Republic of the Congo (DRC) were last conducted from 1981 to 1986. Since then, the population that is immunologically naïve to orthopoxviruses has increased significantly due to cessation of mass smallpox vaccination campaigns. To assess the current risk of infection, we analyzed human monkeypox incidence trends in a monkeypox-enzootic region. Active, population-based surveillance was conducted in nine health zones in central DRC. Epidemiologic data and biological samples were obtained from suspected cases. Cumulative incidence (per 10,000 population) and major determinants of infection were compared with data from active surveillance in similar regions from 1981 to 1986. Between November 2005 and November 2007, 760 laboratory-confirmed human monkeypox cases were identified in participating health zones. The average annual cumulative incidence across zones was 5.53 per 10,000 (2.18-14.42). Factors associated with increased risk of infection included: living in forested areas, male gender, age < 15, and no prior smallpox vaccination. Vaccinated persons had a 5.2-fold lower risk of monkeypox than unvaccinated persons (0.78 vs. 4.05 per 10,000). Comparison of active surveillance data in the same health zone from the 1980s (0.72 per 10,000) and 2006-07 (14.42 per 10,000) suggests a 20-fold increase in human monkeypox incidence. Thirty years after mass smallpox vaccination campaigns ceased, human monkeypox incidence has dramatically increased in rural DRC. Improved surveillance and epidemiological analysis is needed to better assess the public health burden and develop strategies for reducing the risk of wider spread of infection.

Studies on the burden of human monkeypox in the Democratic Republic of the Congo (DRC) were last conducted from 1981 to 1986. Since then, the population that is immunologically naïve to orthopoxviruses has increased significantly due to cessation of mass smallpox vaccination campaigns. To assess the current risk of infection, we analyzed human monkeypox incidence trends in a monkeypox-enzootic region. Active, population-based surveillance was conducted in nine health zones in central DRC. Epidemiologic data and biological samples were obtained from suspected cases. Cumulative incidence (per 10,000 population) and major determinants of infection were compared with data from active surveillance in similar regions from 1981 to 1986. Between November 2005 and November 2007, 760 laboratory-confirmed human monkeypox cases were identified in participating health zones. The average annual cumulative incidence across zones was 5.53 per 10,000 (2.18–14.42). Factors associated with increased risk of infection included: living in forested areas, male gender, age < 15, and no prior smallpox vaccination. Vaccinated persons had a 5.2-fold lower risk of monkeypox than unvaccinated persons (0.78 vs. 4.05 per 10,000). Comparison of active surveillance data in the same health zone from the 1980s (0.72 per 10,000) and 2006–07 (14.42 per 10,000) suggests a 20-fold increase in human monkeypox incidence. Thirty years after mass smallpox vaccination campaigns ceased, human monkeypox incidence has dramatically increased in rural DRC. Improved surveillance and epidemiological analysis is needed to better assess the public health burden and develop strategies for reducing the risk of wider spread of infection.