Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector

Abstract

Rotaviruses (RVs) are important enteric pathogens of newborn humans and animals, causing diarrhea and in rare cases death, especially in very young individuals. Rotavirus vaccines presently used are modified live vaccines that lack complete biological safety. Previous work from our laboratory suggested that vaccines based on in situ produced, non-infectious rotavirus-like particles (RVLPs) are efficient while being entirely safe. However, using either vaccine, active mucosal immunization cannot induce protective immunity in newborns due to their immature immune system. We therefore hypothesized that offspring from vaccinated dams are passively immunized either by transfer of maternal antibodies during pregnancy or by taking up antibodies from milk. Using a codon optimized polycistronic gene expression cassette packaged into herpesvirus particles, the simultaneous expression of the RV capsid genes led to the intracellular formation of RVLPs in various cell lines. Vaccinated dams developed a strong RV specific IgG antibody response determined in sera and milk of both mother and pups. Moreover, sera of naïve pups nursed by vaccinated dams also had RV specific antibodies suggesting a lactogenic transfer of antibodies. Although full protection of pups was not achieved in this mouse model, our observations are important for the development of improved vaccines against RV in humans as well as in various animal species.

Maternal Immunization: New Perspectives on Its Application Against Non-Infectious Related Diseases in Newborns

“…Moreover, new antenatal vaccines that are designed to potentially control infections driven by major neonatal pathogens, such as group B streptococcus, respiratory syncytial virus and cytomegalovirus, are currently in the developmental phase [ 34 , 35 , 36 , 37 , 38 ] and included in ongoing or completed clinical trials (GBS: [ 39 , 40 ]; RSV: [ 41 ], NCT02247726, NCT02624947; CMV: [ 36 ], NCT00133497). Other vaccines against Rotavirus and Vibrio Cholerae are under investigation for antenatal application [ 42 , 43 ]. More recently, the concern about the harmful results on the fetal brain caused by Zika virus exposure during pregnancy [ 44 , 45 ] triggered the effort to develop a new vaccine for pregnant women, stirring up the debate about the necessity and safety to include pregnant woman in maternal immunization clinical trials [ 45 ].…”

Correlative STED super-resolution light and electron microscopy on resin sections

“…CLEM has been used to find rare events by using the fluorescence signal to identify these events and guiding the EM for detailed structural analysis [2,3]. Likewise, CLEM has been used to combine information about specific protein localisations using light microscopy with the contextual information about surrounding cellular membranes and structures using electron microscopy [4][5][6]. This has become even more important in the light of the new diffraction unlimited superresolution techniques which enable the localisation of fluorescent markers with molecular precision, thereby closing the gap between light and electron microscopic resolution.…”

Application of Transmission Electron Microscopy Techniques in the Veterinary Diagnosis of Viral Gastroenteritis in Livestock Animals

“…Resin embedding technique allowed to study several ultrastructural aspects of the intracellular behavior of the TGEV in intestinal fragments of infected pigs [108] and of the parvovirus in intestinal fragments of newborn dogs with diarrhea [220].This technique also allows studying the efficiency of the vaccines based on in situ produced, noninfectious rotavirus-like particles (RVLPs) [221].…”