SARS vaccines: where are we?

Rachel L. Roper; Kristina E. Rehm


Expert Rev Vaccines. 2009;8(7):887-898. 

In This Article

Vaccine Enhancement of Disease

The greatest fear among vaccinologists is the creation of a vaccine that is not only ineffective, but which exacerbates disease. Unfortunately, CoV vaccines have a history of enhancing disease, notably with feline CoVs.[80,125] While several mechanisms may exist, the best understood is antibody-mediated entry of virus into cells via immunoglobulin Fc receptors. This has been demonstrated to occur for the SARS-CoV S protein in human B-cell lines,[126] however, the same group showed that SARS-CoV S protein-vaccinated animals showed no signs of enhanced lung pathology or hepatitis, and indeed that the viral load was reduced following challenge with SARS-CoV; although hamsters may not respond in a way similar to humans immunologically.[126] Other groups have also shown that administration of anti-S antibody does not enhance disease upon SARS-CoV challenge in mice or ferrets,[78] again suggesting that antibody is not enhancing disease in SARS-CoV infection.

There have only been two reports of possible vaccine-induced pathology in SARS vaccine trials to date. In one study, ferrets vaccinated with the poxvirus vector MVA expressing SARS-CoV S protein displayed increased liver pathology after challenge[63] compared to other groups, but liver pathology has not been increased with any other SARS-CoV vaccines. In our ferret vaccine trials using S and N proteins, we noted a delayed histopathology in vaccinated groups, but no increase in pathology compared to unvaccinated groups.[52] The lack of vaccine enhancement of disease is further supported by a recent study in WKV-vaccinated and challenged ferrets that were followed for 3 weeks;[53] however, the exact details and combination of vaccine vector and antigen may control this phenomenon. In the other study that raised vaccine safety concerns, vaccination with the N protein expressed in Venezuelan equine encephalitis virus replicon particles was reported to increase eosinophilic infiltration and damage in lungs of mice challenged with SARS-CoV.[127] This has not been reported in other studies, and in our studies with combination S and N protein expressed in Ad, no eosinophillic infiltration was noted in mice or ferrets.[49,52] While each vaccine and antigenic combination must be thoroughly evaluated for safety and efficacy, the overall picture for SARS-CoV vaccines shows no particular reason for concern with vaccine enhancement of disease. In the cases where it has been reported, it appears to be confined to a particular expression system rather than specifically related to any antigen. In the vast majority of studies, immunogenicity has been elicited without any negative impact on health after challenge with the virulent pathogen.


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