Certain HLA-DR alleles have been associated with predisposition to human rheumatoid arthritis (RA). There is also evidence that certain HLA-DQ alleles may also be important in determining susceptibility to RA. We have previously demonstrated that mice transgenic for HLA-DQ8, a DQ allele associated with susceptibility to RA, develop severe arthritis after type II collagen immunization. To investigate the influence of polymorphic difference at the DQ loci on susceptibility to arthritis, we generated mice transgenic for HLA-DQ6, an allele associated with a nonsusceptible haplotype. The DQ6 mice were found to be resistant to collagen-induced arthritis. We also assessed the combined effect of an RA-susceptible and an RA nonassociated DQ allele by producing double-transgenic mice expressing DQ6 and DQ8 molecules, representing the more prevalent condition found in humans where heterozygosity at the DQ allele is common. The double-transgenic mice developed moderate CIA when immunized with CII when compared with the severe arthritis observed in DQ8 transgenic mice, much like RA patients bearing both susceptible and nonsusceptible HLA haplotypes. These studies support a role for HLA-DQ polymorphism in human RA. (

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Zika virus is an emerging arbovirus of humans in the western hemisphere. With its potential spread into new geographical areas, it is important to define the vector competence of native mosquito species. We tested the vector competency of Aedes vexans (Meigen) from the Lake Agassiz Plain of northwestern Minnesota and northeastern North Dakota. Aedes aegypti (L.) was used as a positive control for comparison. Mosquitoes were fed blood containing Zika virus and 2 wk later were tested for viral infection and dissemination. Aedes vexans (n = 60) were susceptible to midgut infection (28% infection rate) but displayed a fairly restrictive midgut escape barrier (3% dissemination rate). Cofed Ae. aegypti (n = 22) displayed significantly higher rates of midgut infection (61%) and dissemination (22%). To test virus transmission, mosquitoes were inoculated with virus and 16-17 d later, tested for their ability to transmit virus into fluid-filled capillary tubes. Unexpectedly, the transmission rate was significantly higher for Ae. vexans (34%, n = 47) than for Ae. aegypti (5%, n = 22). The overall transmission potential for Ae. vexans to transmit Zika virus was 1%. Because of its wide geographic distribution, often extreme abundance, and aggressive human biting activity, Ae. vexans could serve as a potential vector for Zika virus in northern latitudes where the conventional vectors, Ae. aegypti and Ae. albopictus Skuse, cannot survive. However, Zika virus is a primate virus and humans are the only amplifying host species in northern latitudes. To serve as a vector of Zika virus, Ae. vexans must feed repeatedly on humans. Defining the propensity of Ae. vexans to feed repeatedly on humans will be key to understanding its role as a potential vector of Zika virus.

Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA) for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000). Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50). Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8), or no-treatment (n=8), developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral biological product capable of preventing a lethal disease when administered post-exposure.

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