SARS vaccines: where are we?

Rachel L. Roper; Kristina E. Rehm

Disclosures

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

In This Article

Subunit Vaccines: Antigen Targets & Trials

Subunit vaccines comprised of purified antigen are advantageous owing to their safety and simplicity; however, protective efficacy is sometimes lacking. In particular, exogenously produced proteins are typically presented with MHC class II and thus often do not generate robust cytotoxic T-cell responses. CoV S proteins are the favorite targets in CoV subunit vaccine development since this viral protein contains determinants known to elicit protective immune responses.[73,74] Consequently, the SARS-CoV S glycoprotein, shown to be responsible for receptor binding to cellular ACE2, is an attractive target for the development of both vaccine and therapeutics.[75,76] This approach is strongly supported by the finding that a human monoclonal antibody that binds to the N-terminal of S protein potently neutralizes SARS-CoV infection and inhibits syncytia formation through blocking of receptor binding.[77] Moreover, the S protein has been shown to induce serum-neutralizing antibodies and confer protective immunity against SARS-CoV challenge in mice and African green monkeys.[62,64,78] Since several other proteins are also expressed on the surface of the virion (Figure 1) and elicit antibodies detectable in sera of convalescent SARS patients,[35] other proteins may also be useful to augment protective immunity. For example, antibodies to M proteins have also been shown to have neutralizing activity.[79] In addition, it has also been shown that SARS-CoV S protein can generate CD4 and CD8 T-cell responses.[37]

Studies from other animal CoV vaccines have also shown that the CoV N protein may represent another antigen candidate for vaccine development.[27,80] Although antibodies to CoV N proteins have no virus-neutralizing activity in vitro,[79] there is evidence that the protein may provide in vivo protection by induction of cell-mediated immunity,[73,81,82] as it has been shown to generate CoV-specific CD8+ T cells[82,83,84,85] and provide protection in animals following infection.[84,86] The expressed SARS-CoV N protein has been shown to be a vaccine candidate by inducing antigen-specific T-cell responses, but no in vivo protection experiments were performed with these vaccines.[87,88] A review was published recently addressing the progress in subunit vaccines.[89]

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