Evaluation of a Zika virus-like particle-based vaccine in a highly penetrant non-human primate model of congenital infection

@article{jaeger2026evaluation,
  title = {{Evaluation of a Zika virus-like particle-based vaccine in a highly penetrant non-human primate model of congenital infection}},
  author = {Hannah K. Jaeger and Jessica L. Smith and Caralyn S. Labriola and Lydia J. Pung and Olivia L. Hagen and Michael Denton and Rahul J. D’Mello and Christopher J. Parkins and Whitney C. Weber and Samuel Medica and Craig N. Kreklywich and Victor R. DeFilippis and Stephen Bondoc and Kathleen Busman-Sahay and Jenna N. Castro and Gavin Zilverberg and Riely White and Margaret Terry and Aaron M. Barber-Axthelm and Michael K. Axthelm and Jeremy Smedley and Matthew T. Aliota and Andrea M. Weiler and Thomas C. Friedrich and Jacob Estes and Terry K. Morgan and Jamie O. Lo and Victoria H. J. Roberts and Daniel N. Streblow and Alec J. Hirsch},
  journal = {PLOS Neglected Tropical Diseases},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pntd.0014692},
  url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014692},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Evaluation of a Zika virus-like particle-based vaccine in a highly penetrant non-human primate model of congenital infection
AU  - Hannah K. Jaeger
AU  - Jessica L. Smith
AU  - Caralyn S. Labriola
AU  - Lydia J. Pung
AU  - Olivia L. Hagen
AU  - Michael Denton
AU  - Rahul J. D’Mello
AU  - Christopher J. Parkins
AU  - Whitney C. Weber
AU  - Samuel Medica
AU  - Craig N. Kreklywich
AU  - Victor R. DeFilippis
AU  - Stephen Bondoc
AU  - Kathleen Busman-Sahay
AU  - Jenna N. Castro
AU  - Gavin Zilverberg
AU  - Riely White
AU  - Margaret Terry
AU  - Aaron M. Barber-Axthelm
AU  - Michael K. Axthelm
AU  - Jeremy Smedley
AU  - Matthew T. Aliota
AU  - Andrea M. Weiler
AU  - Thomas C. Friedrich
AU  - Jacob Estes
AU  - Terry K. Morgan
AU  - Jamie O. Lo
AU  - Victoria H. J. Roberts
AU  - Daniel N. Streblow
AU  - Alec J. Hirsch
PY  - 2026
DA  - 2026/09/08
JO  - PLOS Neglected Tropical Diseases
DO  - 10.1371/journal.pntd.0014692
UR  - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014692
AB  - 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.
SN  - 1935-2735
ER  -