SARS

Five years after the first severe acute respiratory syndrome (SARS) outbreak, several candidate SARS-coronavirus (CoV) vaccines are at various stages of preclinical and clinical development. Based on the observation that SARSCoV infection is efficiently controlled upon passive transfer of antibodies directed against the spike (S) protein of SARS-CoV, vaccines containing the S protein have been formulated. Animals immunized with inactivated whole virus vaccines or live-recombinant vaccines expressing the SARS-CoV S protein (e.g., using rabies virus, vesicular stomatitis virus, bovine parainfluenza virus type 3, adenovirus, or attenuated vaccinia virus MVA as a vector), as well as mice immunized with DNA vaccines expressing the S protein gene all developed neutralizing antibodies to SARS-CoV and were protected against SARS-CoV challenge.Although much effort has been focused on developing a SARS vaccine, the commercial viability of such a vaccine for SARS-CoV will ultimately depend on whether the virus re-emerges in the near future. This vaccine should induce highly cross-reactive neutralizing antibodies to protect against newly emerging viruses related to SARS-CoV and protect both the gastrointestinal and respiratory tract in the absence of significant side effects. Given the fact that in the previous outbreak mainly the elderly succumbed to the infection, special attention should be given to vaccines that are able to efficiently protect aged individuals

Authors' response to Hogan

In response to our Perspective on nonhuman primate models for SARS, which accompanied the article by Lawler et al., Robert Hogan questions the usefulness of nonhuman primates as good models for SARS.As demonstrated by several groups, SARS coronavirus (SARS-CoV) replicates to high titers in the respiratory tract of a surprisingly broad range of animal species, albeit showing remarkable differences in cell tropism. We have argued that efficient infection of type 1 and 2 pneumocytes as seen in macaques and humans—most likely due to the similarities in the spike protein binding domains of the host SARS-CoV receptor ACE2—is a prerequisite for the SARS-CoV infection–induced pathology observed in humans. So far there is no strong evidence that a similar tropism is observed in other animal species.[...

Authors' response to Hogan

In response to our Perspective on nonhuman primate models for SARS, which accompanied the article by Lawler et al., Robert Hogan questions the usefulness of nonhuman primates as good models for SARS.As demonstrated by several groups, SARS coronavirus (SARS-CoV) replicates to high titers in the respiratory tract of a surprisingly broad range of animal species, albeit showing remarkable differences in cell tropism. We have argued that efficient infection of type 1 and 2 pneumocytes as seen in macaques and humans—most likely due to the similarities in the spike protein binding domains of the host SARS-CoV receptor ACE2—is a prerequisite for the SARS-CoV infection–induced pathology observed in humans. So far there is no strong evidence that a similar tropism is observed in other animal species.[...

The application of genomics to emerging zoonotic viral diseases

Interspecies transmission of pathogens may result in the emergence of new infectious diseases in humans as well as in domestic and wild animals. Genomics tools such as high-throughput sequencing, mRNA expression profiling, and microarray-based analysis of single nucleotide polymorphisms are providing unprecedented ways to analyze the diversity of the genomes of emerging pathogens as well as the molecular basis of the host response to them. By comparing and contrasting the outcomes of an emerging infection with those of closely related pathogens in different but related host species, we can further delineate the various host pathways determining the outcome of zoonotic transmission and adaptation to the newly inva

Comparative Pathogenesis of Severe Acute Respiratory Syndrome Coronaviruses

Over the last two decades the world has witnessed the global spread of two genetically related highly pathogenic coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, the impact of these outbreaks differed significantly with respect to the hospitalizations and fatalities seen worldwide. While many studies have been performed recently on SARS-CoV-2, a comparative pathogenesis analysis with SARS-CoV may further provide critical insights into the mechanisms of disease that drive coronavirus-induced respiratory disease. In this review, we comprehensively describe clinical and experimental observations related to transmission and pathogenesis of SARS-CoV-2 in comparison with SARS-CoV, focusing on human, animal, and in vitro studies. By deciphering the similarities and disparities of SARS-CoV and SARS-CoV-2, in terms of transmission and pathogenesis mechanisms, we offer insights into the divergent characteristics of these two viruses. This information may also be relevant to assessing potential novel introductions of genetically related highly pathogenic coronaviruses.</p

Antigenic evolution of SARS coronavirus 2

SARS coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, emerged in China in December 2019. Vaccines developed were very effective initially, however, the virus has shown remarkable evolution with multiple variants spreading globally over the last three years. Nowadays, newly emerging Omicron lineages are gaining substitutions at a fast rate, resulting in escape from neutralization by antibodies that target the Spike protein. Tools to map the impact of substitutions on the further antigenic evolution of SARS-CoV-2, such as antigenic cartography, may be helpful to update SARS-CoV-2 vaccines. In this review, we focus on the antigenic evolution of SARS-CoV-2, highlighting the impact of Spike protein substitutions individually and in combination on immune escape.</p

Comparative Pathogenesis of Severe Acute Respiratory Syndrome Coronaviruses

Over the last two decades the world has witnessed the global spread of two genetically related highly pathogenic coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, the impact of these outbreaks differed significantly with respect to the hospitalizations and fatalities seen worldwide. While many studies have been performed recently on SARS-CoV-2, a comparative pathogenesis analysis with SARS-CoV may further provide critical insights into the mechanisms of disease that drive coronavirus-induced respiratory disease. In this review, we comprehensively describe clinical and experimental observations related to transmission and pathogenesis of SARS-CoV-2 in comparison with SARS-CoV, focusing on human, animal, and in vitro studies. By deciphering the similarities and disparities of SARS-CoV and SARS-CoV-2, in terms of transmission and pathogenesis mechanisms, we offer insights into the divergent characteristics of these two viruses. This information may also be relevant to assessing potential novel introductions of genetically related highly pathogenic coronaviruses.</p