Experimental animal model for analyzing immunobiological responses following vaccination with formalin‐inactivated respiratory syncytial virus

Abstract

Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine was developed in the 1960s. However, this vaccine does not prevent infection in RSV-na€ ıve recipients and has the paradoxical effect of increasing the severity of RSV illness following natural infection, which has been a major obstacle to developing RSV vaccines. Several experimental animal models for determining the cause of the severe symptoms in FI-RSV recipients have been developed. In the present study, cotton rats immunized with FI-RSV were challenged with RSV and histopathological findings and recovery of infectious virus were studied. Copy numbers of mRNA of Th1 and Th2 cytokines were measured in lung tissues to gain better understanding of their immune responses. Infiltration of inflammatory cells and prominent interstitial pneumonitis were observed in the FI-RSV group, as was induction of mRNA of Th2 cytokines such as IL-4, IL-10, IL-13 and RANTES. Rats immunized with recombinant measles virus expressing the RSV F protein (MVAIK/RSV/F) and those treated with anti-RSV mAb (palivizumab) showed very mild interstitial pneumonitis. Amounts of mRNA of IL-1b, IFN-g and IL-4 were higher in the MVAIK/RSV/F group. Administration of palivizumab before RSV challenge decreased the severity of interstitial pneumonitis in the FI-RSV group. FI-RSV induced skewed Th2 responses, resulting in severe inflammatory responses.

Protection of calves by a prefusion-stabilized bovine RSV F vaccine

“…Furthermore, pulmonary eosinophilia, which has been associated with vaccine-ERD in infants, calves, and mice, 11 , 37 , 38 was not seen in either group of vaccinated calves, even though bRSV was isolated from the BAL of all calves that had been vaccinated with post-F bRSV F. ERD in mice and cotton rats vaccinated with formalin-inactivated virus or purified F protein is associated with virus replication in the lungs, induction of a Th2-biased cytokine response and low affinity, poorly neutralizing antibodies. 38 – 40 Although the T-cell response was not analyzed in the present study, the Montanide TM ISA 71G adjuvant used was designed to increase Th1 responses in veterinary species.…”

Cotton rat model for testing vaccines and antivirals against respiratory syncytial virus

“…Reports of preclinical testing of many of these candidates in the cotton rat model have been published in the past three years ( Table 1 ). These candidates include live attenuated RSV strains modified by codon-deoptimization and modification/replacement of RSV NS, SH, F, and G genes, 26 , 27 virus-vectored vaccines expressing RSV F or G protein from the backbone of modified parainfluenza 5, 28 , 29 measles, 30 adenoviruses 26 and 35 76 , or Sendai viruses; 31 DNA-plasmid-vectored vaccines, 32 virus-like particles (VLPs) alone, or in combination with DNA boost, 33 – 36 adjuvanted subunit vaccines, 37 – 39 and whole-virus inactivated preparations. 40 …”

Current Animal Models for Understanding the Pathology Caused by the Respiratory Syncytial Virus

“…This feature has greatly hindered the development of an exclusive animal model, and therefore, the choice of the more suitable animal model required for each researcher will depend strongly on the aspect of the infection that needs to be studied and the investigative hypothesis proposed (Jorquera et al., 2016). The most commonly used animals have been rodents, such as mice (Graham et al., 1988; Bueno et al., 2008) and cotton rats (Prince et al., 1978, 1983; Sawada and Nakayama, 2016); ruminants (Elvander, 1996; Woolums et al., 1999, 2004; Meyerholz et al., 2004; Derscheid and Ackermann, 2012; Ackermann, 2014); and non-human primates (Kakuk et al., 1993; Szentiks et al., 2009), but at the present, the diversification of animal models is a requirement for addressing the diverse problematics of this viral infection and the development of vaccines and treatments. For this reason, the objective of this article is to review the several animal models used and their applications and to discuss their pros and cons.…”