Nu havde jeg jo læst det link, Steve, og bad jo netop derfor om et link til den <i>verdensomspændende konklusionen fra 2016 om at man ikke kan finde en vaccine </i>
Jeg forklarede jo sågar hvordan Oxford-vaccinen passede ind med det du linkede, men det kan selvfølgelig være du ikke har læst det du sendte, så tillad mig at citere fra fra det du sendte.
Vectored vaccines are generally based on vectors with a proven safety record. These vaccines allow production and release of immunogenic antigens from infected cells for a limited period of time. Vectors based on viruses from different families (poxvirus, adenovirus, measles, and togavirus (VEE)) have been used in the development of vaccines for CoVs. In the case of MERS-CoV, the most advanced and promising candidate is the modified vaccinia virus Ankara (MVA), a viral vector that does not replicate in mammalian cells and, therefore, holds great promise as a vaccine platform (Altenburg et al., 2014, Haagmans et al., 2016, Song et al., 2013, Volz et al., 2015). Using this vector, S protein fragments of different length were expressed: full-length, extracellular S1 domain, or the RBD. In all cases, neutralizing antibodies and T-cell responses for MERS-CoV were induced. One of these vectors induced mucosal immunity and reduced the shedding of MERS-CoV by a factor of one thousand after challenge with the virulent virus in dromedary camels, thus preventing spread from the animal reservoir (Haagmans et al., 2016). An MVA-vectored vaccine will be entering clinical trials in 2016 supported by the German Center for Infection Research (DZIF) (Paddock, 2015).
A second, more advanced vectored vaccine is based on recombinant adenovirus expressing S protein fragments of different size (Guo et al., 2015, Kim et al., 2014, Shim et al., 2012). Sublingual immunization with a recombinant adenovirus encoding SARS-CoV S protein induced systemic and mucosal immunity in a mouse model system (Shim et al., 2012). Systemic and mucosal immunity were also elicited in mice by single immunization with human adenovirus type 5 or 41 vector-based vaccines carrying the S protein of MERS-CoV (Guo et al., 2015). Whether or not, these immune responses confer protection against viral infection remains to be evaluated.
Immunization with measles virus vectors expressing the SARS-CoV S protein induced neutralizing antibodies and strong Th1-biased responses, a hallmark of live-attenuated viruses and a highly desirable feature for an antiviral vaccine (Escriou et al., 2014), though eradication of measles virus may represent an obstacle for the application of this type of vaccines. VEE replicon particles expressing the SARS-CoV S protein provided protection against lethal homologous and heterologous challenge in an aged mice model (Sheahan et al., 2011).
Therefore, in principle, several well-known vectors offer the possibility of protection against CoV infection. Although these vectors are based on live viruses with a reasonable record of safety, they are limited to presenting one or a reduced number of CoV antigens to the immune system, in contrast to live vaccines based on the whole, attenuated CoV
An alternative approach to the design of attenuated viruses as vaccine candidates that several laboratories have followed is the identification of virulence-associated viral genes (DeDiego et al., 2014a, Stobart and Moore, 2015, Totura and Baric, 2012) that, in many cases, encode nonessential immunomodulatory proteins. Modification or deletion of these genes leads to the generation of attenuated viruses that may be useful as vaccine candidates. Our laboratory has used this strategy extensively to generate CoV vaccines. Also, other groups have used this approach successfully to produce vaccine candidates for influenza, respiratory syncytial virus, measles, dengue, and mumps (Kirkpatrick et al., 2016, Stobart and Moore, 2015).
Engineering attenuated CoVs as vaccine candidates requires the availability of reverse-genetics systems suitable to introduce deletions of (or mutations in) virulence genes as well as appropriate animal models for the evaluation of efficacy and safety of these candidate vaccines. To date, no vaccines have been developed for common human CoV infections. Nevertheless, infectious cDNA clones have been engineered for the three human CoVs that can be efficiently propagated in tissue culture: HCoV-229E, HCoV-OC43, and HCoV-NL63 (Donaldson et al., 2008, St-Jean et al., 2006, Thiel et al., 2001). Similarly, infectious cDNA clones have been generated for SARS-CoV (Almazan et al., 2000, Yount et al., 2003) and MERS-CoV (Almazan et al., 2013, Scobey et al., 2013), providing an excellent basis for the rational development of live-attenuated vaccines based on recombinant viruses.