Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus

Abstract

BackgroundSevere acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease.DesignFour candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated IM on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology.ResultsAll vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence.ConclusionsThese SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.

Porcine gastroenteric viruses: pathogenesis and protection

“…Subunit vaccines and those based in inactivated viruses, at least in the case of CoVs, have clear advantages, such as fast development and being stable (Jaume et al, 2012;Tseng et al, 2012;Wang et al, 2014b). At the same time, these vaccines also have well documented, important limitations, such as inducing non-lasting memory, eosinophilia and antibody dependent enhancement of the infectivity (ADEI) (Bolles et al, 2011;Iwata-Yoshikawa et al, 2014;Tseng et al, 2012).…”

How Prepared Are We to Control Severe Acute Respiratory Syndrome in Future

“…Studies related to SARS vaccinehave taught us several lessons about pathogenesis and host responses to SARS-CoV, in addition to unraveling the need for caution. With certain experimental vaccines, such as the viral vector based ones, immunopathology and redirection of the viral vector to brain was reported (Czub et al, 2005;Deming et al, 2006;Kam et al, 2007;Jaume et al, 2011;Tseng et al, 2012). Subsequent studies demonstrated that a sub lingual immunization can prevent the viral vector entry into the brain (Shim et al, 2012).…”

“…(Lin et al, 2007). Hypersensitive appropriate animal model (See et al, 2008) reaction upon post-immunization viral challenge in mice (Kam et al, 2007;Tseng et al, 2012) Recombinant vector Disease exacerbation upon SARS-CoV Protective in mice, ferrets, monkeys, Vaccines (Adenovirus, challenge in some cases (Czub et al, 2005) hamsters (Bukreyev et al, 2004; Poxvirus or recombinant) See et al, 2006;Napoli et al, 2007;See et al, 2008) …”

“…Immunopathology is observed in some cases Protective in hamsters and ferrets particle vaccines (Kam et al, 2007;Jaume et al, 2011;(Kam et al, 2007;Tseng et al, 2012) Tseng et al, 2012. Hypersensitive reaction upon post-immunization viral challenge in mice (Kam et al, 2007;Tseng et al, 2012) DNA vaccines Safe and immunogenic in healthy humans Protective in mice (Yang et al, 2004) (Martin et al, 2008).…”

“…Hypersensitive reaction upon post-immunization viral challenge in mice (Kam et al, 2007;Tseng et al, 2012) DNA vaccines Safe and immunogenic in healthy humans Protective in mice (Yang et al, 2004) (Martin et al, 2008). Hypersensitive reaction upon post-immunization viral challenge in mice (Kam et al, 2007;Tseng et al, 2012) Attenuated vaccines Safety needs to be established E protein lacking-or ExoN mutant vaccine is immunogenic and efficacious Graham et al, 2012) …”