Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by b-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection. (Marra et al., 2003;Rota et al., 2003) and by experimental infection of macaques to fulfil Koch's postulates . 0008-1579 G 2006 SGM Printed in Great BritainCurrently, there is no effective treatment for SARS. Prevention through contact-reduction or transmission-blocking measures has been the only means available to modify the devastating impact of this illness. Prevention through vaccination would be an attractive alternative that is less reliant on individual case detection to be effective. No vaccines are currently licensed for any of the human CoVs, but effective vaccines have been produced for some animal CoVs, such as certain strains of Infectious bronchitis virus (poultry), Bovine coronavirus and Canine coronavirus (Cavanagh, 2003;Enjuanes et al., 1995;Pratelli et al., 2003;Saif, 2004;Takamura et al., 2002). Individuals convalescing from SARS develop high titres of neutralizing antibodies (Tan et al., 2004) and the appearance of antibodies coincides with the onset of resolution of SARS pneumonia Woo et al., 2004). Thus, there is some optimism that an effective vaccine against SARS-CoV may also be possible.Coronavirus spike (S) proteins have long been known to be a major determinant in coronavirus pathogenesis, given that this viral protein interacts with cellular receptors as well as con...

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage. INTRODUCTIONSevere acute respiratory syndrome (SARS) caused 8098 reported cases and 774 deaths in 26 countries (WHO, 2004a) in a single autumn-to-spring period from 2002 to 2003, and had significant effects on the global economy. Serological evidence suggests zoonotic transmission of SARS coronavirus (CoV) into the human population for several years before this outbreak (Zheng et al., 2004); transmission to humans has continued, resulting in at least four independent non-laboratory associated cases in (Che et al., 2006Fleck, 2004; Guan et al., 2005; WHO, 2004b). The aetiological agent of SARS has been identified as a novel human CoV by sequencing of its genome (Marra et al., 2003;Rota et al., 2003) and by experimental infection of macaques to fulfil Koch's postulates (Fouchier et al., 2003). It is of particular concern as a zoonosis because it can replicate in a large number of animals including cats, pigs, ferrets, foxes, monkeys and rats (Chen et al., 2005; et al., 1996;Olsen, 1993). Although antibodies to CoV N proteins have no virus-neutralizing activity, there is evidence that the protein may provide protection in vivo by induction of cell-mediated immunity, although it has also been suggested to induce eosinophilic infiltrates resulting in immunopathology (Deming et al., 2006;Enjuanes et al., 1995; Stohlman et al., 1995;Wesseling et al., 1993). N protein has been shown to generate CoV-specific CD8 + T cells (Boots et al., 1991;Seo et al., 1997; Stohlman et al., 1993 Stohlman et al., , 1995; it also provides protection in animals in response to infection by animal CoV (Collisson et al., 2000;Seo et al., 1997). In addition, vaccination with SARS N protein decre...

Nearly a year after the classification of the COVID-19 outbreak as a global pandemic, it is clear that different factors have contributed to an increase in psychological disorders, including public health measures that infringe on personal freedoms, growing financial losses, and conflicting messages. This study examined the evolution of psychosocial impacts with the progression of the pandemic in adult populations from different countries and continents, and identified, among a wide range of individual and country-level factors, which ones are contributing to this evolving psychological response. An online survey was conducted in May/June 2020 and in November 2020, among a sample of 17,833 adults (Phase 1: 8806; Phase 2: 9027) from eight countries/regions (Canada, the United States, England, Switzerland, Belgium, Hong Kong, the Philippines, New Zealand). Probable generalized anxiety disorder (GAD) and major depressive episode (MDE) were assessed. The independent role of potential factors was examined using multilevel logistic regression. Probable GAD or MDE was indicated by 30.1% and 32.5% of the respondents during phases 1 and 2, respectively (a 7.9% increase over time), with an important variation according to countries/regions (range from 22.3% in Switzerland to 38.8% in the Philippines). This proportion exceeded 50% among young adults (18–24 years old) in all countries except for Switzerland. Beyond young age, several factors negatively influenced mental health in times of pandemic; important factors were found, including weak sense of coherence (adjusted odds ratio aOR = 3.89), false beliefs (aOR = 2.33), and self-isolation/quarantine (aOR = 2.01). The world has entered a new era dominated by psychological suffering and rising demand for mental health interventions, along a continuum from health promotion to specialized healthcare. More than ever, we need to innovate and build interventions aimed at strengthening key protective factors, such as sense of coherence, in the fight against the adversity caused by the concurrent pandemic and infodemic.