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Updated: Nov 19, 2025
An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Repeated Dose Toxicity Study and Developmental and Reproductive Toxicology Studies of a Respiratory Syncytial Virus
Alan H Stokes1, Kelle Franklin2, Daniel E Fisher3
1GSK, Rockville, MD, USA.
Insights
This study shows the Respiratory Syncytial Virus (RSV)PreF3 vaccine is safe for mothers and infants, and older adults. The RSV vaccine demonstrated no adverse effects on reproductive health or offspring development.
Area of Science:
- Vaccinology
- Immunology
- Preclinical Development
Background:
- Respiratory Syncytial Virus (RSV) is a significant cause of respiratory infections, necessitating effective vaccines for vulnerable populations like young children and older adults.
- GSK's candidate RSV vaccine utilizes a recombinant RSVPreF3 protein in its prefusion conformation, with tailored approaches for different age groups.
- Vaccine strategies differ: pregnant mothers receive unadjuvanted RSVPreF3 for infant protection via maternal antibodies, while older adults receive AS01-adjuvanted RSVPreF3 for a stronger immune response.
Purpose of the Study:
- To evaluate the local and systemic effects of the RSVPreF3 vaccine in a repeated dose toxicity study.
- To assess the impact of the unadjuvanted RSVPreF3 vaccine on female reproductive function and offspring development in preclinical models.
Main Methods:
- Repeated dose toxicity studies were conducted in rabbits using intramuscular injections of unadjuvanted, AS01-adjuvanted, or coadministered RSVPreF3 vaccine.
- Female fertility, embryo-fetal development, and postnatal development were evaluated in rats and rabbits following administration of the unadjuvanted RSVPreF3 vaccine.
Main Results:
- In rabbits, intramuscular RSVPreF3 vaccine injections resulted in expected inflammatory reactions consistent with vaccine response.
- Studies in rats and rabbits indicated no adverse effects of the unadjuvanted RSVPreF3 vaccine on female fertility, pregnancy, delivery, lactation, or offspring development.
Conclusions:
- The RSVPreF3 vaccine candidate is well-tolerated both locally and systemically.
- The vaccine demonstrated a favorable safety profile regarding female reproductive function and pre- and postnatal development in preclinical studies.
Abstract:
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections, and vaccines are needed to treat young children and older adults. One of GSK's candidate vaccines for RSV contains recombinant RSVPreF3 protein maintained in the prefusion conformation. The differences in immune function of young children and older adults potentially require different vaccine approaches. For young children, anti-RSV immunity can be afforded during the first months of life by vaccinating the pregnant mother during the third trimester with unadjuvanted RSVPreF3, which results in protection of the infant due to the transplacental passage of anti-RSV maternal antibodies. For older adults with a waning immune response, the approach is to adjuvant the RSVPreF3 vaccine with AS01 to elicit a more robust immune response.The local and systemic effects of biweekly intramuscular injections of the RSVPreF3 vaccine (unadjuvanted, adjuvanted with AS01, or coadministered with a diphtheria-tetanus-acellular pertussis vaccine) was tested in a repeated dose toxicity study in rabbits. After three intramuscular doses, the only changes observed were those commonly related to a vaccine-elicited inflammatory reaction. Subsequently, the effects of unadjuvanted RSVPreF3 vaccine on female fertility, embryo-fetal, and postnatal development of offspring were evaluated in rats and rabbits. There were no effects on pregnancy, delivery, lactation, or the pre- and postnatal development of offspring.In conclusion, the RSVPreF3 vaccine was well-tolerated locally and systemically and was not associated with any adverse effects on female reproductive function or on the pre- and postnatal growth and development of offspring.
