A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

Abstract

A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV) infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

The humanized DRAGA mouse (HLA-A2. HLA-DR4. RAG1 KO. IL-2R g c KO. NOD) establishes inducible and transmissible models for influenza type A infections

“…24 Both DRAG and DRAGA mouse strains were shown to respond to several pathogens with specific human IgM and IgG antibodies. [24][25][26][27][28] Our data indicate that the DRAGA mouse is a viable model for studies of human-like lung physiopathology, and of humoral and cellular immune responses to infections with IAVs such as A/H1N1/PR8 and A/H3N2 subtypes of Aichi, Victoria and Hong Kong viruses.…”

“…22,23 Both DRAG and DRAGA mice responded by specific antibodies to infection or immunization with malaria protozoans, HIV, ZIKA, malaria protozoan, influenza A/ H1N1 PR8 virus, 24 and scrub typhus. [25][26][27][28] Although various wild-type and humanized mouse models have been described for a number of viral infections (i.e., HIV, EBV, HCV, HBV, HCMV, DENV, HTL-1, HSV-2, HuNoV, JVC, Scrub typhus, ZIKA virus) and bacterial or parasitic infections (i.e., Plasmodium falciparum, Leishmania, Neisseria meningitides, Salmonella Typhi, Borrelia herrmesii, Streptococcus agalactiae group B sepsis, and Scrub Typhus), 18 HIS-humanized animal models for infections with influenza type A infections (IAV) of groups 1 and 2 have not been established yet.…”

A Hitchhiker's guide to humanized mice: new pathways to studying viral infections

“…These data elucidate that within this model, the main reservoir of the virus focuses primarily on B cells and myeloid‐derived cells, particularly monocytes. In addition to this, a Zika virus prM and E protein encoding vaccine has also been demonstrated to show efficacy in humanized mice and to elicit protein‐E‐specific antibody production alongside neutralizing antibodies, following 6 weeks of immunization …”

“…Recent publications from Yi et al 91 described the first humanized mouse infections with Zika virus. NSG-HLA-DR4 mice engrafted with a human immune system from an allogeneic DR4 + HSC donor are reportedly susceptible to Zika virus infection.…”

“…In addition to this, a Zika virus prM and E protein encoding vaccine has also been demonstrated to show efficacy in humanized mice and to elicit protein-Especific antibody production alongside neutralizing antibodies, following 6 weeks of immunization. 91…”