Pandemics-Born Revolution in the Preclinical and Clinical Trials of Microbial Vaccines

Dear Colleagues,

Until December 2019, we were living in the world of successfully functioning vaccines and vaccination programs. New vaccines based on the “naked” nucleic acids, RNA as well as DNA, recognized as promising more than 20 years ago, were not implemented due to our conservatism and cautiousness. The conservative approach to vaccine development was forcibly ended by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that urgently required the recruitment of  all available vaccine platforms, both classic and new ones. 

Among the important challenges in the clinical trials of COVID-19 vaccines was the race against an increasing proportion of people who had previously had an asymptomatic infection, which complicated the recruitment of study participants and the assessment of the results of the trials. Multiple emergences of new virus variants demanded (and still demand) repeated trials of protectivity. The application of vaccines based on mRNA relied on the establishment of complicated worldwide distribution lines. Despite the difficulties, a multitude of “old-fashioned” and novel vaccine types effectively protecting against COVID-19 morbidity and mortality was established. The unprecedented speed of the roll out of these vaccines has shown what can be achieved with global support and commitment, as well as unprecedented funding and institutional support worldwide, which altogether helped to address challenges in the vaccine development process from the lab bench to global distribution. It also highlighted the role of vaccines in the prevention of the disease or reducing disease severity, motivating support to vaccinology as the science that works for people. Our rapid response to the SARS-CoV-2 pandemic was largely possible due to the as-of-yet unused developments in the vaccine research, with their rapid licensing alongside fast development of the large-scale manufacturing technologies. The success in our fight against the pandemic demonstrated the importance of preparedness to new and re-emerging infections, from the development of early vaccine candidates to Phase III clinical trials and massive vaccine production for global use. 

The application of the new vaccine platforms will surely facilitate further rapid development of new (and improved old) vaccines, with respect to both preclinical and clinical trials. This raises the question of whether we should focus our efforts on the broad use of the platforms rolled out for COVID-19, such as mRNA or vectored vaccines, to the new true or perceived pathogen challenges? Enthusiasts suggest that we should apply these platforms to create new-generation vaccines against common infections for which we already have well-functioning vaccines. A more balanced opinion suggests that although the new vaccine platforms have shown remarkable safety and protectivity against COVID-19, reproduction of the success against any other pathogen would take a huge effort, as it did for COVID-19, turning replacement into a highly resource-craving enterprise. 

Among the important difficulties in preclinical COVID-19 vaccine candidate protectivity assessment was the lack of a universal animal model, reproducing all aspects of the infection, including sites of replication and all stages of direct virus-associated and subsequent immune-associated pathogenesis. Because of this, vaccine candidate testing required costly simultaneous use of several laboratory animal models, each having its advantages and drawbacks. Once again, this demonstrated the need to develop reliable (sometimes multiple) animal models for any given pathogen for in vivo trials of both safety and efficacy. Furthermore, the pandemic encouraged health care specialists, research society, and even the general public to realize that the efficacy of antimicrobial drugs and vaccines, as well as their safety, cannot be reliably tested in vitro, despite our efforts to follow the 3R principles of animal research (Replace, Reduce, Refine). 

At the same time, even the best animal models do not guarantee success in human application. Lengthy and laborious clinical trials are needed to prove vaccine safety and demonstrate its efficacy. Pandemics raise the question of whether it is legitimate to truncate/shorten standard clinical trials, assessing safety and efficacy in the case of an emergency.  Moreover, is it acceptable to test the efficacy of vaccines via human pathogen–challenge tests. Before the pandemic, this was only done for influenza. We do not yet know whether the future will give us more examples.

This Special Issue welcomes submissions of experimental papers, short communications, reviews and activity reports focusing on the above problems. We specifically welcome submissions, which consider the impact of the SARS-CoV-2 pandemic on:

• Development of plug and play platforms approach;
• Future vaccine discovery/development harnessing the current momentum for vaccine development to create new vaccine platforms;
• Novel vaccines/technologies for accommodating emerging SARS-CoV-2 variants;
• Novel vaccines/technologies against other common and emerging (re-emerging) pathogens;
• Development of animal models to test vaccine efficacy;
• Vaccine manufacture and upscale now and in the future; 
• Formulations that aid the stability of vaccines facilitating distribution to less accessible and low resource countries;
• All aspects addressing vaccine acceptance and hesitancy. 

A special invitation to submit is addressed to the participants of the international conference “Vaccines and vaccination during and post COVID pandemics” held online from December 7–9, 2022 at Riga Stradins University, Riga, Latvia, sponsored by VACCINES. Information on the event can be viewed at the website of Riga Stradins University https://www.rsu.lv/en/vac-vac-2022.

Dr. Maria G. Isaguliants
Prof. Dr. Felicity Jane Burt
Dr. Ilya Gordeychuk
Guest Editors

Manuscript Submission Information

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• DNA vaccines
• RNA vaccines
• recombinant viral vaccines
• vaccination techniques
• vaccine carriers
• adjuvants
• vaccine complications, adverse effects
• vaccines against acute viral infections
• vaccines against chronic viral infections
• vaccines against microbial infections
• vaccines against parasitic infections
• cancer vaccines
• animal models
• vaccine safety tests