Beijing time on April 1st, the current vaccine against the new coronavirus (SARS-CoV-2) ? We can find a variety of articles and posts on the Internet to try to answer this question. However, no vaccine for the new coronavirus has been approved, and although several companies have announced that they are developing a candidate vaccine, these are unlikely to play an important role in the current outbreak.
In the United States, candidate vaccines cannot pass appropriate preclinical and clinical trials, as well as regulatory and production processes, in just a few weeks. In general, the cost of developing a vaccine can be as high as $1 billion or more in non-explosive situations, and it can often take years to get approval. Having said that, in the event of an outbreak, we can make some concessions, and the medical community is doing better and better in developing platform technology, making it faster and faster to develop more viable candidate vaccines.
Globally, the SARS-CoV-2 treatment pipeline includes about 15 potential vaccine candidates. These vaccines use a variety of techniques, involving different media such as DNA, messenger RNA (mRNA), nanoparticles, synthetic and modified viral particles.
There are two main vaccine candidates being developed in the United States, from Inovio Pharmaceuticals inc. and Moderna Therapeutics Inc. (in partnership with the National Institute of Allergy and Infectious Diseases (NIAID). Both vaccines rely on specific mechanisms for “platform technology”. In other words, both vaccines are made up of a primary nuclear structure (in this case RNA or DNA), which can be used against a variety of different viruses by inserting a sequence of related genes from the virus of interest. This structure acts as a platform for more effective development of vaccine candidates to fight emerging viruses such as SARS-CoV-2.
Both candidate vaccines are partially funded by the Alliance for Innovation in Epidemic Prevention (CEPI), a global partnership of the public, private, charitable and civil society organizations that has the resources to quickly track new infectious disease vaccines and access them during outbreaks. While most candidate vaccines may take a year or more to begin clinical trials in Phase I, those funded by CEPI may speed up the time frame for the market.
Inovio Pharmaceuticals’ vaccine is a DNA-based vaccine that is currently in preclinical development, and Phase I trials are expected to take place in the coming months. Phase I clinical trials typically require 20 to 100 healthy volunteers to assess the vaccine’s safety and determine the desired dose by giving them a candidate vaccine.
The vaccine, developed by Moderna and NIAID, is a messenger RNA vaccine. Typically, the mRNA vaccine contains an open reading box (ORF) for the target antigen, with a non-translation zone (UTRs) with a polyadedetide tail on either side. Theoretically, the mRNA vaccine is translated into instantaneous expression that drives antigens after vaccination, thus promoting an immune response.
Recently, Moderna stepped up research and development efforts and sent the vaccine to NIAID to begin the phase I trial to test the vaccine’s safety and immunogenicity. The trial is expected to begin at the end of April and preliminary results will be announced in July or August. In January, Moderna spent a lot of time developing and preparing vaccines after learning about the genetic sequence of the new coronavirus from Chinese scientists. After the 2002 SARS-CoV outbreak in China, it took NIAID about 20 months to get the vaccine into Phase I human clinical trials, said Anthony Fauci, director of NIAID.
However, it remains unclear whether Moderna’s candidate vaccine will trigger an adequate immune response to effectively fight SARS-CoV-2. The premise of gene-based platform technology is that it is able to function against fragments in the viral genome that are involved in stimulating the host’s immune response. Although we can make informed choices about the sequencethat that causes immunogenicity, we do not know whether the best sequence was selected until the human trial is complete. Thus, it can be said that there is no precedent for such vaccines, and no human vaccines using gene-based technology have been approved.
Virologist Jose Esparza commented on Moderna’s candidate vaccine, “The rapid production of RNA vaccines is great. However, preclinical trials are important for assessing safety before small-scale Phase I clinical trials can be carefully conducted in human volunteers. In particular, it is important to note that an infectious enhancement of antibody dependence may occur, which is caused by antibody binding rather than neutralizing. “
In fact, rapid development of vaccines and upcoming Phase I clinical trials do not guarantee their effectiveness. We won’t know until after human trials that the sequence chosen by Moderna and NIAID can trigger enough immune responses to protect the body. And even if the initial results are encouraging, the vaccine may not be widely used in the general public until 2021, as late clinical trials and regulation are required.
Author: Helen Stillwell is an assistant researcher at David Hafler’s Immunobiology Laboratory at Yale University. (Any day)