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Pre-conception maternal rotavirus exposure induces long term effects on her offspring’s adaptive immune response to RV infection

van Dijl, Sharne (2021) MOBN03 20202
Degree Projects in Molecular Biology
Popular Abstract
Maternal Rotavirus antibodies inhibit rotavirus specific B cell responses in offspring

For infants, the period following birth is marked by a developmentally immature immune system and increasing exposure to pathogens, however it is also a period in which maternally derived antibodies are still present in the neonate. These antibodies are obtained during pregnancy through the placenta and following birth for the duration of nursing. It is within this period that various vaccines such as the rotavirus (RV) vaccine are administered. Rotavirus infects the absorptive villi in the small intestine, resulting in malabsorptive diarrhoea due to cell damage and destruction. In low-income countries, RV vaccine efficacy is low and in various... (More)
Maternal Rotavirus antibodies inhibit rotavirus specific B cell responses in offspring

For infants, the period following birth is marked by a developmentally immature immune system and increasing exposure to pathogens, however it is also a period in which maternally derived antibodies are still present in the neonate. These antibodies are obtained during pregnancy through the placenta and following birth for the duration of nursing. It is within this period that various vaccines such as the rotavirus (RV) vaccine are administered. Rotavirus infects the absorptive villi in the small intestine, resulting in malabsorptive diarrhoea due to cell damage and destruction. In low-income countries, RV vaccine efficacy is low and in various infection models, maternally derived antibodies have been shown to alter the offspring immune response to infection and vaccination. As the disease burden in low-income countries remains high (Fig. 1), pre-conception exposure to RV is likely. We therefore aimed to experimentally determine how the pathogen-specific immune response to RV infection in offspring is altered when dams have been exposed to RV pre-conception. This was achieved using mice, in which dams which were exposed to RV pre-conception and the RV specific immune responses to subsequent RV infection in pups analysed.

Antibodies, produced by B cells, can protect mice from RV infection if they recognize the virus. Upon infection of the pups, we analysed the immune cell composition of the small intestine and the intestine draining lymph node (mLN) through flow cytometry and found that RV infected pups mounted a general B cell response, which was not specific to the virus if the pups were protected by mother-derived antibodies (Fig. 2A and B). RV specific CD8+ T cells however, needed to kill infected cells once infection established, were present and largely unaffected by maternal antibodies. Through cross-fostering (raising of pups from naïve mothers by previously infected mothers and vice versa), we demonstrated that placentally transferred antibodies were not as strongly inhibiting to the RV specific B cell generation as antibodies in breastmilk. Mice from RV-dams could be reinfected post-weaning and resulted in a B cell response to secondary infection that was highly reduced. Therefore, maternal antibodies in breastmilk inhibit the generation of RV specific B cell-driven immunity, and this inhibition results in long term alterations to the secondary responses following reinfection

Master’s Degree Project in Molecular Biology 60 credits 2021
Department of Biology, Lund University

Supervisor: Katharina Lahl (PI) & Konjit Muleta (P.hD student)
Biomedical Centre, LU/Department of Immunology (Less)
Please use this url to cite or link to this publication:
author
van Dijl, Sharne
supervisor
organization
course
MOBN03 20202
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9067514
date added to LUP
2021-11-02 11:03:38
date last changed
2021-11-02 11:03:38
@misc{9067514,
  author       = {{van Dijl, Sharne}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Pre-conception maternal rotavirus exposure induces long term effects on her offspring’s adaptive immune response to RV infection}},
  year         = {{2021}},
}