{ "abstract": "Zika virus (ZIKV) is an arthropod-borne Orthoflavivirus that caused a major outbreak in Central and South America in 2015–16. During that outbreak, ZIKV infection during pregnancy was associated with high rates of adverse outcomes, including miscarriage and a spectrum of neurological birth defects collectively termed congenital Zika syndrome (CZS). Ten years later, there are still no licensed ZIKV vaccines, underscoring the need for robust experimental models to evaluate vaccine efficacy against congenital disease. Here, we evaluated a highly pathogenic nonhuman primate pregnancy model for its ability to assess vaccine-mediated protection using a Zika virus-like particle (VLP) vaccine as a test platform. First, non-pregnant rhesus macaques (RM) were vaccinated with a prime-boost method to compare control, VLP alone, and VLP plus Alhydrogel (alum) adjuvant. Vaccination plus alum elicited strong neutralizing antibody responses and reduced viral dissemination compared to controls. Next, we evaluated the vaccine’s protective efficacy against adverse pregnancy complications. Two cohorts of female RM were vaccinated with ZIKV-VLP adjuvanted with alum or alum alone prior to time-mated breeding. At gestational day (GD) 30 (mid first trimester), pregnant animals were challenged with ZIKV-DAK 41524, an African-lineage strain previously shown to induce frequent first-trimester pregnancy loss. Within the vaccinated cohort, two of three animals reached the study endpoint of GD 90 with no observed adverse pregnancy outcomes. One vaccinated animal experienced early pregnancy loss despite the absence of detectable virus in fetal or placental tissues. In the sham vaccine control pregnancy cohort, severe adverse outcomes included miscarriage and hydrops fetalis with widespread viral RNA and placental pathology in two animals. These results support a high risk of early pregnancy loss following African-lineage ZIKV-DAK 41524 infection in RM. This model can be further used to understand the complexities of placental immunological features underlying miscarriage following ZIKV infection. Author summary: Zika virus (ZIKV) infection during pregnancy is associated with pregnancy loss, severe birth defects, including microcephaly and developmental delays, and other subtle neurologic changes. Although vaccine development efforts have been ongoing since the 2015/2016 ZIKV outbreak, no approved vaccine is currently available. Many existing studies have tested vaccines in animal models using strains such as ZIKV-PRVABC59 that cause mild or moderate pregnancy complications at similar rates to human cases. Using challenge strains that only cause mild, or moderate pregnancy complications makes it difficult to rigorously evaluate vaccine efficacy. To address this gap, we evaluated a highly pathogenic nonhuman primate pregnancy model for its ability to test vaccine performance under stringent conditions. We used a virus-like particle (VLP) vaccine, a safe and effective method for use during pregnancy as it is replication-deficient and only contains viral structural antigens, as a platform to test this model. We found that the VLP vaccine, when paired with an adjuvant (alum), induced strong antibody responses in mice and controlled viral dissemination following challenge in nonpregnant rhesus macaques (RM). To evaluate vaccine performance during pregnancy, we used a model of ZIKV infection during early gestation in RM that is associated with high rates of fetal demise. In pregnant macaques, the vaccine reduced maternal viremia, limited viral spread to fetal and placental tissues, and conferred partial protection against virus-mediated adverse outcomes and placental damage. This study establishes a high-stringency RM pregnancy model of ZIKV vaccine-challenge that will be valuable for evaluating future vaccine and prevention strategies against ZIKV congenital disease and early pregnancy loss.", "abstract_shown": true, "affiliations": [ "The Vaccine & Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America", "Division of Pathobiology & Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America", "Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America", "Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, United States of America", "Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America", "Department of Pathobiological Sciences, School of Veterinary Medicine and Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America", "Department of Pathology, Oregon Health & Science University, Portland, Oregon, United States of America" ], "article_type": "Research Article", "arxiv": null, "author_total": 30, "authors": [ { "affs": [ 0 ], "name": "Hannah K. Jaeger" }, { "affs": [ 1 ], "name": "Jessica L. Smith" }, { "affs": [ 2 ], "name": "Caralyn S. Labriola" }, { "affs": [ 3 ], "name": "Lydia J. Pung" }, { "affs": [ 4 ], "name": "Olivia L. Hagen" }, { "affs": [ 5 ], "name": "Michael Denton" }, { "affs": [ 6 ], "name": "Rahul J. D’Mello" }, { "name": "Christopher J. Parkins" }, { "name": "Whitney C. Weber" }, { "name": "Samuel Medica" }, { "name": "Craig N. Kreklywich" }, { "name": "Victor R. DeFilippis" }, { "name": "Stephen Bondoc" }, { "name": "Kathleen Busman-Sahay" }, { "name": "Jenna N. Castro" }, { "name": "Gavin Zilverberg" }, { "name": "Riely White" }, { "name": "Margaret Terry" }, { "name": "Aaron M. Barber-Axthelm" }, { "name": "Michael K. Axthelm" }, { "name": "Jeremy Smedley" }, { "name": "Matthew T. Aliota" }, { "name": "Andrea M. Weiler" }, { "name": "Thomas C. Friedrich" }, { "name": "Jacob Estes" }, { "name": "Terry K. Morgan" }, { "name": "Jamie O. Lo" }, { "name": "Victoria H. J. Roberts" }, { "name": "Daniel N. Streblow" }, { "name": "Alec J. Hirsch" } ], "bibtex": "https://research.draconitic.com/paper/7r7b2bkm9kqg0.bib", "cited_by": 0, "doi": "10.1371/journal.pntd.0014692", "fulltext_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014692", "id": "7r7b2bkm9kqg0", "issns": [ "1935-2735" ], "landing_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014692", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2739|Mosquito-borne diseases and control" ], [ "plos", "/Biology and life sciences/Anatomy/Reproductive system/Placenta" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Developmental biology/Embryology/Placenta" ], [ "plos", "/Biology and life sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Flaviviruses/Zika virus" ], [ "plos", "/Biology and life sciences/Microbiology/Virology/Viral vaccines" ], [ "plos", "/Biology and life sciences/Organisms/Eukaryota/Animals/Vertebrates/Amniotes/Mammals/Primates/Monkeys/Old World monkeys/Macaque" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/RNA viruses/Flaviviruses/Zika virus" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Flaviviruses/Zika virus" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Antibodies" ], [ "plos", "/Biology and life sciences/Zoology/Animals/Vertebrates/Amniotes/Mammals/Primates/Monkeys/Old World monkeys/Macaque" ], [ "plos", "/Medicine and health sciences/Anatomy/Reproductive system/Placenta" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Infectious disease control/Vaccines/Viral vaccines" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Viral diseases/Viremia" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Flaviviruses/Zika virus" ], [ "plos", "/Medicine and health sciences/Women's health/Maternal health/Pregnancy" ], [ "plos", "/Medicine and health sciences/Women's health/Obstetrics and gynecology/Pregnancy" ], [ "plos", "/Research and analysis methods/Immunologic techniques/Immunoassays/Enzyme-linked immunoassays" ] ], "openalex": "W7211934675", "pdf_url": "https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0014692&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-08", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/7r7b2bkm9kqg0.ris", "sources": [ { "first_seen": "2026-10-30T12:17:56Z", "native_id": "10.1371/journal.pntd.0014692", "source": "plos", "url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014692" } ], "subjects": [ { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "biology", "origin": "plos:microbiology", "subfield": "microbiology" }, { "field": "medicine", "origin": "plos:anatomy", "subfield": "physiology" } ], "title": "Evaluation of a Zika virus-like particle-based vaccine in a highly penetrant non-human primate model of congenital infection", "title_text": "Evaluation of a Zika virus-like particle-based vaccine in a highly penetrant non-human primate model of congenital infection", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:56Z", "url": "https://research.draconitic.com/paper/7r7b2bkm9kqg0", "venue": "PLOS Neglected Tropical Diseases", "versions": [] }