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Updated: Jun 17, 2026
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
Exploring offspring behaviour after prenatal COVID-19 vaccination in mice
Lilla Otrokocsi1, Fruzsina Maácz1,2, Pál Tod1
1Laboratory of Molecular Pharmacology, HUN-REN Institute of Experimental Medicine, Budapest, 1083, Hungary.
Insights
Prenatal COVID-19 vaccination did not cause autism spectrum disorder (ASD)-like behaviors in mice. Influenza vaccination showed mild, temporary effects, suggesting no widespread neurodevelopmental disruption from these vaccines during pregnancy.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Maternal immunization transfers antibodies to offspring, protecting them from infection.
- The long-term neurodevelopmental effects of prenatal vaccination, including for COVID-19 and influenza, require further investigation.
- Autism spectrum disorder (ASD) is a neurodevelopmental condition with social and behavioral alterations.
Purpose of the Study:
- To evaluate the impact of prenatal exposure to COVID-19 mRNA (BNT162b2) and influenza vaccines on neurodevelopment and autism-related behaviors in juvenile and adult mice.
- To assess maternal and fetal immune responses, including cytokine, P2X7 receptor, BDNF, CRP, and lipid peroxidation levels.
- To compare vaccine effects with a positive control (poly(I:C)) known to induce inflammation and neurodevelopmental changes.
Main Methods:
- Mice were exposed prenatally to COVID-19 mRNA vaccine, influenza vaccine, or poly(I:C).
- Offspring behavior was assessed at 4 and 8 weeks using tests like the elevated plus maze and open field.
- Maternal plasma and fetal brain tissues were analyzed for immune markers (cytokines, CRP), neurotrophic factors (BDNF), and lipid peroxidation.
Main Results:
- Prenatal COVID-19 vaccination caused mild, transient maternal cytokine increases but no fetal brain inflammation. Offspring showed minor, age/sex-dependent behavioral changes, without a clear ASD phenotype.
- Prenatal influenza vaccination induced mild, age-dependent behavioral alterations (e.g., circling, reduced sociability) without detectable maternal/fetal inflammation.
- Maternal poly(I:C) induced robust inflammation and significant fetal brain effects, including elevated cytokines, CRP, P2X7 receptor, and reduced adult BDNF.
Conclusions:
- Prenatal COVID-19 vaccination did not result in persistent ASD-like phenotypes or widespread neurodevelopmental alterations in this mouse model.
- Prenatal influenza vaccination had limited and transient behavioral effects.
- These findings suggest that, within this experimental model, maternal vaccination against COVID-19 and influenza does not lead to significant long-term neurodevelopmental disruption.
Abstract:
Maternal immunisation allows the transfer of protective antibodies to the offspring, reducing the risk of severe infection during early life. While vaccination during pregnancy is clinically recommended, its long-term impact on neurodevelopment remains under investigation. Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by social and behavioural alterations. Here, we evaluated whether prenatal exposure to the COVID-19 mRNA BNT162b2 vaccine or influenza vaccine affects general and autism-related behavioural outcomes in juvenile (4 weeks) and adult (8 weeks) mouse offspring. We also assessed maternal and fetal immune responses by measuring cytokines, soluble P2X7 receptor, BDNF, CRP, and lipid peroxidation in maternal plasma and fetal brain tissue. Prenatal COVID-19 vaccination elicited a moderate maternal cytokine response (increased IL-6 and KC) without overt fetal brain inflammation. Mild, age- and sex-dependent behavioural changes were observed, including anxiety-related parameters in the elevated plus maze and altered locomotion in the open field at 4-8 weeks, however, no consistent or robust ASD-like behavioural phenotype emerged across ages. Fetal P2X7 receptor levels were elevated, while fetal CRP, BDNF, and TBARS remained unchanged. In adult offspring, BDNF was selectively reduced in the prefrontal cortex, whereas hippocampal BDNF and P2X7 receptor levels in both regions were unaffected. Although embryonic P2X7 receptor levels were transiently elevated following COVID-19 vaccination, these changes were not accompanied by fetal inflammation or persistent adult purinergic alterations. Prenatal influenza vaccination induced mild, age-dependent behavioural alterations, such as increased circling in juveniles and reduced sociability in females, without detectable maternal or fetal inflammatory responses or changes in fetal neurotrophic markers. In contrast, maternal poly(I:C) administration provoked robust systemic inflammation and pronounced fetal brain effects, including elevated cytokines, CRP, P2X7 receptor, and region-specific microglial density, accompanied by persistent reductions in adult BDNF expression. Overall, within the limits of this experimental design, prenatal COVID-19 vaccination did not produce long-lasting ASD-like phenotypes or widespread neurodevelopmental alterations, while influenza vaccination had limited and transient effects. These findings are consistent with the absence of widespread or persistent neurodevelopmental disruption in this experimental model, although further studies-including multiple doses, gestational timepoints, and cellular-level analyses-are warranted to fully elucidate mechanisms and long-term outcomes.
