Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells in Vitro, Ex Vivo and in Vivo

Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies

Patients with primary immunodeficiencies are a reservoir of poliovirus and a risk to polio eradication

ABSTARCT: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame. Keywords: Poliovirus eradication, Immunodeficiency-associated vaccine-derived polioviruses, Oral poliovirus vaccine, Humoral immunodeficiency, Combined immunodeficiency, Primary immunodeficienc

Nature’s nations: the shared conservation history of Canada and the USA

Historians often study the history of conservation within the confines of national borders, concentrating on the bureaucratic and political manifestations of policy within individual governments. Even studies of the popular expression of conservationist ideas are generally limited to the national or sub-national (province, state, etc.) scale. This paper suggests that conservationist discourse, policy and practice in Canada and the USA were the products of a significant cross-border movement of ideas and initiatives derived from common European sources. In addition, the historical development of common approaches to conservation in North America suggests, contrary to common assumptions, that Canada did not always lag behind the USA in terms of policy innovation. The basic tenets of conservation (i.e. state control over resource, class-based disdain for subsistence hunters and utilitarian approaches to resource management) have instead developed at similar time periods and along parallel ideological paths in Canada and the USA

Stopping poliovirus vaccination after eradication: issues and challenges

Since 1988 reported polio cases worldwide have declined by about 85% and the number of known or suspected polioendemic countries has decreased from over 120 to less than 50. With eradication of poliomyelitis approaching, issues potentially affecting when and how vaccination against poliovirus can be stopped become extremely important. Because of the potential risks and benefits inherent in such a decision, the best available science, a risk-benefit analysis, contingency plans, a stock pile of poliovirus vaccines, and the endorsement by the global policy-making committees will all be needed before vaccination can be discontinued. The scientific basis for stopping polio immunization has been reviewed by WHO. This Round Table article summarizes the current state of knowledge, provides an update on the processes and timelines for certification, containment, and stopping vaccination, and highlights some of the unanswered scientific questions that will be addressed by further research. These include whether transmission of vaccine-derived poliovirus strains could be sustained so that poliomyelitis could re-emerge in a future unvaccinated population and whether prolonged excretion of vaccine-derived poliovirus from individuals with immune deficiencies could be a mechanism through which this could occur

A study evaluating poliovirus antibodies and risk factors associated with polio seropositivity in low socioeconomic areas of Pakistan

Background: Seroprevalence studies provide important data on performance of immunization programs, susceptible groups and populations at-risk of future outbreaks. Identifying risk factors that affect seroconversion of the oral polio vaccine (OPV) will enable the polio eradication initiatives to increase seroprevalence. This paper describes the first population-based seroprevalence survey in Pakistan. Methods: This study evaluated the seroprevalence of poliovirus (PV) types 1, 2, and 3 antibodies to OPV in an illustrative sample of 554 subjects 6–11 months of age in three geographic locations of Pakistan (Lahore, Karachi, and Peshawar) representing a low socioeconomic at-risk populations. Antibody titers were measured and sero protection rates and geometric median titers were compared among different geographic regions and populations, as were demographics and OPV vaccination history collected by questionnaire. Univariate and multivariate analyses were conducted on subject characteristics to assess for potential risk factors for failure to sero-convert. Results: The average seroprevalence of PV1, PV2, and PV3 was 96.0%, 87.9% and 86.7%, respectively. The lowest sero protection rate for all three serotypes was for Karachi with 90.2%, 73.8%, and 78.8% for PV1, PV2, and PV3, respectively. Significant regional variation in PV3 seroprevalence was found (range: 74.2–100%). In the univariate analysis, age, total and campaign OPV doses were associated with higher seroprevalence, whereas stunting, respondent education and diarrhea in the past six months were significant risk factors for failure to sero-convert. Conclusions: These findings demonstrate consistently high levels of antibody response to PV1 and more geographically varied response to PV2 and PV3. Additionally, important risk factors affecting seropositivity were identified