Correlative outcomes of maternal immunization against RSV in cotton rats

Abstract

Maternal anti-respiratory syncytial virus (RSV) antibodies protect neonates from RSV disease throughout first weeks of life. Previous studies of maternal immunization in cotton rats showed that a single immunization during pregnancy of RSV-primed dams with virus-like particles (VLPs) assembled with pre-fusion F protein and the wild type G protein boosted their RSV serum antibody concentration and protected pups early in life against RSV challenge. We extended these findings by evaluating responses to RSV infection in litters from two consecutive pregnancies of immunized dams. Using an RSV-primed population of VLP-vaccinated and unvaccinated dams, we defined correlations between dams’ and litters’ RSV neutralizing antibodies (NA); between litters’ NA and protection; and between litter’s NA and their lung expression of selected cytokines, of a first or of a second pregnancy. Lung pathology was also evaluated. We found positive correlation between the NA titers in the dams at delivery and the NA in their first and second litters and negative correlations between the litters’ NA and protection from RSV challenge. Vaccination of dams modulated the mRNA expression for IFNγ and IL-6 and lung pathology in the first and in the second litter at different times after birth, even in the absence of detectable NA. Maternal RSV vaccination enhanced the levels of antibodies transferred to offspring and their protection from challenge. Importantly, maternal vaccination also impacted the immunological and inflammatory response of the offspring’s lungs well into maturity, and after the antiviral effect of maternally transferred NA waned or was no longer detectable.

Virus-like Particle Vaccine Expressing the Respiratory Syncytial Virus Pre-Fusion and G Proteins Confers Protection against RSV Challenge Infection

“…VLPs co-expressing both F and G antigens induced virus-specific antibodies that contributed to protection and also limited the inflammation [ 26 ]. Immunizing cotton rat dams with VLPs expressing the RSV Pre-F and G antigens enabled the transmission of neutralizing antibodies to their offspring and ensured that they were well-protected [ 27 ]. The co-expression of both antigens was also reported to be crucial for mounting enhanced immune response to the RSV F glycoprotein [ 28 ].…”

Exacerbated lung inflammation following secondary RSV exposure is CD4+ T cell-dependent and is not mitigated in infant BALB/c mice born to PreF-vaccinated dams

“…In a similar model of maternal RSV immunization using cotton rats, Blanco et al. demonstrated that high titers of neutralizing matAb correlated with complete protection from viral challenge while also reducing the expression of the inflammatory cytokines, IFNγ and IL-6, and associated lung pathology ( 12 ). Collectively, these studies demonstrate that anti-RSV immunity in infants is influenced by the presence of highly neutralizing matAb.…”

Respiratory Syncytial Virus Maternal Vaccination in Infants below 6 Months of Age: Meta-Analysis of Safety, Immunogenicity, and Efficacy

“…Similarly, the F-based RSV vaccine was shown to be immunogenic to ameliorate antibody levels in recipients, including non-pregnant healthy women [24] and specific populations, e.g., the elderly and children [25]. A growing body of research in vivo also demonstrated how passive immunization of the offspring by administering F-based RSV jab to the dams is helpful to promote MatAbs, in both the dams and their offspring [26][27][28].…”