Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice

Abstract

Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that the anti-viral immune response in the pregnant host was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8 T cells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. These insights underscore the importance of influenza vaccination compliance in pregnant women and may open novel therapeutic avenues.

A Measles Virus-Based Vaccine Candidate Mediates Protection against Zika Virus in an Allogeneic Mouse Pregnancy Model

“…After vaccination in the standard regimen (32), immunized females were mated with BALB/c males to mimic the natural genetic heterozygosity between mothers and fetuses. A similar system has been successfully applied to assess the effects of influenza A virus infection on unborn offspring (40) and most recently also for the effects of intrauterine ZIKV infection on newborn animals and their development (41). Challenging these pregnant mice revealed the teratogenic effects of ZIKV infection, including the intrauterine growth retardation observed previously in a model that also takes advantage of the heterozygous IFN-␣/␤ receptor status of pups in IFNAR-deficient dams and a closely related challenge virus, ZIKV strain H/PF/2013 (42).…”

“…For analysis of cellular immune responses, mice were vaccinated as described above, and spleens were isolated on day 35. For challenge experiments, female IFNAR Ϫ/Ϫ -CD46Ge mice were vaccinated as described above, and 21 days after the boost vaccination, the vaccinated mice were mated allogeneically with male BALB/c mice in a 1:2 or 1:1 scheme for one night (40). Successful mating was verified by plug check on the following day.…”

Prevalence of intestinal cestode infections of conventionally maintained laboratory (albino) and house mice in Kalar district / Sulaymaniyah province

“…It is a family of cyclophyllidean cestodes, which involves 37 species belonging to seven genera and they are parasites of rodent (host specific) and were not found to infect humans, reviewed in Haukisalmi et al (2018). Significant differences were observed in female than in male (P= 0.045), could be related to suppressed immune response of female during pregnancy (Engels et al 2017). There is an apparent lack of morphological guides for the diagnoses of species belonging to this family (Haukisalmi et al 2018).…”

Immunobiological aspects of vaccines in pregnancy: Maternal perspective

“…Enhanced natural killer (NK) cell and T cell responses to influenza infection were observed in pregnant as compared to non-pregnant women, suggesting that suppression of cell-mediated immune responses is unlikely to be a major contributor to disease severity [11]. Mouse studies suggest a role for impaired migration of anti-viral CD8 T lymphocytes to the lungs [12]. Increased proinflammatory responses of monocytes and dendritic cells to in vitro influenza infection were observed in pregnant as compared to non-pregnant women, suggesting a role for immunopathologic responses [13].…”