Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine.

Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine-associated disease.

Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines.

Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in , , or ). Adverse reactions to the YF vaccine have remained unexplained.

Defining the interval for monitoring potential adverse events following immunization (AEFIs) after receipt of live viral vectored vaccines.

Live viral vectors that express heterologous antigens of the target pathogen are being investigated in the development of novel vaccines against serious infectious agents like HIV and Ebola. As some live recombinant vectored vaccines may be replication-competent, a key challenge is defining the length of time for monitoring potential adverse events following immunization (AEFI) in clinical trials and epidemiologic studies. This time period must be chosen with care and based on considerations of pre-clinical and clinical trials data, biological plausibility and practical feasibility.

Tick-borne encephalitis virus in arthropod vectors in the Far East of Russia.

Isolates of tick-borne encephalitis virus (TBEV) from arthropod vectors (ticks and mosquitoes) in the Amur, the Jewish Autonomous and the Sakhalin regions as well as on the Khabarovsk territory of the Far East of Russia were studied. Different proportions of four main tick species of the family Ixodidae: Ixodes persulcatus P. Schulze, 1930; Haemaphysalis concinna Koch, 1844; Haemaphysalis japonica douglasi Nuttall et Warburton, 1915 and Dermacentor silvarum Olenev, 1932 were found in forests and near settlements.

How Did Zika Virus Emerge in the Pacific Islands and Latin America?

The unexpected emergence of Zika virus (ZIKV) in the Pacific Islands and Latin America and its association with congenital Zika virus syndrome (CZVS) (which includes microcephaly) and Guillain-Barré syndrome (GBS) have stimulated wide-ranging research. High densities of susceptible Aedes spp., immunologically naive human populations, global population growth with increased urbanization, and escalation of global transportation of humans and commercial goods carrying vectors and ZIKV undoubtedly enhanced the emergence of ZIKV.

Live virus vaccines based on a vesicular stomatitis virus (VSV) backbone: Standardized template with key considerations for a risk/benefit assessment.

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viral and other microbial pathogens in their genome (so-called "chimeric virus vaccines"). Many such viral vector vaccines are now at various stages of clinical evaluation. Here, we introduce an attenuated form of recombinant vesicular stomatitis virus (rVSV) as a potential chimeric virus vaccine for HIV-1, with implications for use as a vaccine vector for other pathogens.

Unique safety issues associated with virus-vectored vaccines: Potential for and theoretical consequences of recombination with wild type virus strains.

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration.

Adventitious agents and live viral vectored vaccines: Considerations for archiving samples of biological materials for retrospective analysis.

Vaccines are one of the most effective public health medicinal products with an excellent safety record. As vaccines are produced using biological materials, there is a need to safeguard against potential contamination with adventitious agents. Adventitious agents could be inadvertently introduced into a vaccine through starting materials used for production.

Tick-Borne Encephalitis Virus Diversity in Ixodid Ticks and Small Mammals in South-Western Siberia, Russia.

Unlabelled: The persistence of tick-borne encephalitis virus (TBEV) in nature is maintained by numerous species of reservoir hosts, multiple transmissions between vertebrates and invertebrates, and the virus adaptation to its hosts. Our Aim: was to compare TBEV isolates from ticks and small wild mammals to estimate their roles in the circulation of the viral subtypes.

Methods: TBEV isolates from two species of ixodid ticks, four species of rodents, and one species of shrews in the Novosibirsk region, South-Western Siberia, Russia, were analyzed using bioassay, hemagglutination, hemagglutination inhibition, neutralization tests, ELISA, reverse transcription with real-time PCR, and phylogenetic analysis.

Yellow fever vaccine: worthy friend or stealthy foe?

Recognition that the live yellow fever vaccine may rarely be associated with viscerotropic disease (YEL-AVD) has diminished its safety status. However, the vaccine remains the principal tool for limiting the occurrence of yellow fever, making large portions of Africa and South America more habitable. The subject has previously been exhaustively reviewed.

Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector.

Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies.

Can genetic and clinical findings made in a single patient be considered sufficient to establish a causal relationship between genotype and phenotype? We report that up to 49 of the 232 monogenic etiologies (21%) of human primary immunodeficiencies (PIDs) were initially reported in single patients. The ability to incriminate single-gene inborn errors in immunodeficient patients results from the relative ease in validating the disease-causing role of the genotype by in-depth mechanistic studies demonstrating the structural and functional consequences of the mutations using blood samples. The candidate genotype can be causally connected to a clinical phenotype using cellular (leukocytes) or molecular (plasma) substrates.

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG).

Recombinant viral vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines against human pathogens from Ebola to tuberculosis. An increasing number of candidate viral vector vaccines are entering human clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to improve our ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when licensed.

Risk groups for yellow fever vaccine-associated viscerotropic disease (YEL-AVD).

Although previously considered as the safest of the live virus vaccines, reports published since 2001 indicate that live yellow fever virus vaccine can cause a severe, often fatal, multisystemic illness, yellow fever vaccine-associated viscerotropic disease (YEL-AVD), that resembles the disease it was designed to prevent. This review was prompted by the availability of a listing of the cumulative cases of YEL-AVD, insights from a statistical method for analyzing risk factors and re-evaluation of previously published data. The purpose of this review is to identify and analyze risk groups based on gender, age, outcome and predisposing illnesses.

Defining risk groups to yellow fever vaccine-associated viscerotropic disease in the absence of denominator data.

Several risk groups are known for the rare but serious, frequently fatal, viscerotropic reactions following live yellow fever virus vaccine (YEL-AVD). Establishing additional risk groups is hampered by ignorance of the numbers of vaccinees in factor-specific risk groups thus preventing their use as denominators in odds ratios (ORs). Here, we use an equation to calculate ORs using the prevalence of the factor-specific risk group in the population who remain well.

Yellow fever virus vaccine-associated deaths in young women.

Yellow fever vaccine-associated viscerotropic disease is a rare sequela of live-attenuated virus vaccine. Elderly persons and persons who have had thymectomies have increased susceptibility. A review of published and other data suggested a higher than expected number of deaths from yellow fever vaccine-associated viscerotropic disease among women 19-34 years of age without known immunodeficiency.

Architecture of peptidoglycan: more data and more models.

Peptidoglycan forms a net-like sacculus made of glycan strands crosslinked by peptides. The length of the glycan strands and the degree of crosslinkage vary with bacterial species, strains and growth conditions. Several models for the three-dimensional architecture of peptidoglycan have been proposed, some of which have been tested experimentally.