Comparisons of Antibody Populations in Different Pre-Fusion F VLP-Immunized Cotton Rat Dams and Their Offspring.

Lori M Cullen,Marina S Boukhvalova,Trudy G Morrison,Jorge C G Blanco

doi:10.3390/vaccines8010133

Lori M Cullen, Marina S Boukhvalova + Show 2 more

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https://doi.org/10.3390/vaccines8010133

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Abstract

Respiratory syncytial virus (RSV) infection poses a significant risk for infants. Since the direct vaccination of infants is problematic, maternal vaccination may provide a safer, more effective approach to their protection. In the cotton rat (CR) model, we have compared the immunization of pregnant CR dams with virus-like particles assembled with the prototype mutation stabilized pre-fusion F protein, DS-Cav1, as well two alternative mutation stabilized pre-fusion proteins (UC-2 F, UC-3 F) and showed that the alternative pre-fusion F VLPs protected the offspring of immunized dams significantly better than DS-Cav1 F VLPs (Blanco, et al. J. Virol. 93: e00914). Here, we have addressed the reasons for this increased protection by characterizing the specificities of antibodies in the sera of both immunized dams and their offspring. The approach was to measure the levels of total anti-pre-F IgG serum antibodies that would block the binding of representative pre-fusion specific monoclonal antibodies to soluble pre-fusion F protein targets. Strikingly, we found that the sera in most offspring of DS-Cav1 F VLP-immunized dams had no mAb D25-blocking antibodies, although their dams had robust levels. In contrast, all offspring of UC-3 F VLP-immunized dams had robust levels of these D25-blocking antibodies. Both sets of pup sera had significant levels of mAb AM14-blocking antibodies, indicating that all pups received maternal antibodies. A lack of mAb D25-blocking antibodies in the offspring of DS-Cav1 F VLP-immunized dams may account for the lower protection of their pups from challenge compared to the offspring of UC-3 F VLP-immunized dams.

Highlights

Respiratory syncytial virus (RSV) is the most common lower respiratory tract viral pathogen of neonates and infants [1]
We showed that the specificities of the population of antibodies induced in mice by the five different virus-like particle (VLP)-associated pre-fusion F proteins were different as defined by differences in the serum inhibition of binding of representative monoclonal antibodies to the soluble forms of the pre-fusion F protein [18]
Using cotton rats (CR), the preferred animal model for RSV [7,14,31,32], we reported that the immunization of pregnant animals with one of these alternative pre-fusion F VLPs increased their serum-neutralizing antibody (NAb) titers and significantly increased the protection from RSV challenge of their offspring compared to the immunization of dams with DS-Cav1 F VLPs [30]

Summary

Introduction

Respiratory syncytial virus (RSV) is the most common lower respiratory tract viral pathogen of neonates and infants [1]. This virus accounts for 33.1 million acute lower respiratory tract infections, 3.2 million hospitalizations and an estimated yearly mortality of 118,200 for this population [2]. RSV infections are a common cause of infant physician office visits [3]. The use of any licensed RSV vaccine for immunization of infants will be problematic due to safety issues and the immaturity of their immune systems. As a result of these difficulties, maternal immunization for the protection of their offspring is considered a better approach [4,5,6,7,8,9,10,11,12,13,14]

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