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Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic PolyI:C
Published on: March 25, 2016
Maternal transfer of RSV immunity in cotton rats vaccinated during pregnancy
Jorge C G Blanco1, Lioubov M Pletneva1, Raymonde O Oue1
1Sigmovir Biosystems Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, United States.
Insights
Maternal vaccination against Respiratory Syncytial Virus (RSV) in cotton rats enhances antibody transfer to offspring, providing protection against RSV infection. Boosting mothers improved protection, suggesting a viable strategy for infant immunity.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Respiratory Syncytial Virus (RSV) causes significant infant pneumonia and bronchiolitis globally.
- Current lack of an effective RSV vaccine.
- Maternal antibodies offer temporary protection to infants, but methods to extend this immunity are unknown.
Purpose of the Study:
- To develop a cotton rat model for maternal RSV vaccination.
- To assess antibody transfer and protection in offspring following maternal immunization.
- To evaluate methods for enhancing passive immunity against RSV.
Main Methods:
- Inoculating female cotton rats (naïve or primed) with live RSV.
- Quantifying antibody transfer to litters and challenging offspring with RSV.
- Analyzing viral replication, lung inflammation, and cytokine expression.
Main Results:
- High correlation between maternal and pup RSV-neutralizing antibody (NA) titers and protection.
- Passive protection waned significantly by 4 weeks post-birth.
- Parenteral vaccination and boosting of mothers with live RSV maximized NA levels and offspring protection.
- Enhanced protection correlated with reduced lung cytokine expression and pathology.
Conclusions:
- Maternal RSV vaccination in cotton rats effectively transfers immunity to offspring.
- This model can identify vaccine candidates to improve existing immunity and infant protection.
- Boosting maternal immunization enhances protection, offering a potential strategy for infant immunization.
Abstract:
Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. There is currently no RSV vaccine. Although maternal serum antibodies against RSV are efficiently transferred through placenta protecting human infants from RSV-induced disease, this protection is short-lived and the methods for extending and augmenting protection are not known. The objective of this study was to develop an animal model of maternal RSV vaccination using the Sigmodon hispidus cotton rat. Naïve or RSV-primed female cotton rats were inoculated with live RSV and set in breeding pairs. Antibody transfer to the litters was quantified and the offspring were challenged with RSV at different ages for analysis of protection against viral replication and lung inflammation. There was a strong correlation between RSV-neutralizing antibody (NA) titers in cotton rat mothers and their pups, which also correlated with protection of litters against virus challenge. Passive protection was short-lived and strongly reduced in animals at 4 weeks after birth. Protection of litters was significantly enhanced by inoculating mothers parenterally with live RSV and inversely correlated with the expression of lung cytokines and pathology. Importantly, vaccination and boosting of naïve mothers with the live RSV produced the highest levels of NAs. We conclude that maternal vaccination against RSV in the cotton rat can be used to define vaccine preparations that could improve preexistent immunity and induce subsequent transfer of efficient immunity to infants.

