Rapid response platforms, particularly the messenger RNA (mRNA) platform, have changed the landscape of vaccine development, enabling the rapid response to the COVID-19 pandemic, said Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID) on Monday.

Fauci, speaking at the opening of the Global Vaccine and Immunization Research Forum (GVIRF), co-organized by WHO, the Bill & Melinda Gates Foundation, and the NIAID, highlighted the innovations in vaccinology that made the speedy development of COVID-19 vaccines possible.

“There are a number of new technologies that have now really dominated our approach to COVID-19. For example, there’s genetic immunisation using RNA and DNA vaccines,” said Fauci. “We are well aware now of the successes, for example, of the mRNA vaccines.”

Rapid response platforms are systems that can be adapted against different pathogens. In the case of mRNA vaccines, these have been developed over a number of years to address influenza, Zika and rabies and have shown a high level of efficacy against SARS-CoV2. 

The Pfizer/ BioNTech and Moderna SARS-CoV2 vaccines have both had over 95% efficacy against symptomatic COVID-19 and nearly 100% efficacy against severe disease.

“I think it’s fair to say that rapid response platforms have been a revolution in vaccinology over 2020 with COVID-19,” said Melanie Saville, Director of Vaccine Research and Development at the Coalition for Epidemic Preparedness Innovations (CEPI). “These can be further developed and prepared for future outbreaks, epidemics, and pandemics.”

Barney Graham, deputy director of the Vaccine Research Center at NIAID, added that, over the past 12 years in particular, “new technologies have improved our ability to both prepare for and respond to emerging threats, like structural biology protein engineering and rapid platform manufacturing.” 

Prototype Pathogen Approach

Both Graham and Fauci described the prototype pathogen approach to pandemic preparedness vaccine research used at the NIAID. This refers to studying pathogens of a particular group to build on prior experiences and use strategies to inform vaccine design for related viruses.

In developing vaccines for SARS-CoV2, structure-based vaccine designs from Middle East Respiratory Syndrome (MERS-CoV), which is in the family of coronaviruses, were used and “enabled us to rapidly get a successful vaccine, particularly with mRNA [technology],” said Fauci. 

With the technological advances and the unprecedented R&D work conducted over the past year with COVID-19, “I think we’ve probably moved forward a decade…with COVID-19 vaccines being developed in only 300 days, whereas usually, they would take multiple years, if not decades,” said Saville. 

“One thing to point out [is] the speed with which we went from appreciating the new virus, in this case SARS-CoV2, on January 10 of 2020, to starting a phase one trial, about 65 days later, a phase 3 trial both with Moderna and with Pfizer, on 27 July and now having both vaccines already being administered here in the United States and elsewhere. [This is] the fastest in the history of vaccinology from the identification of a particular pathogen to the actual administration of a vaccine,” said Fauci.

Challenges with mRNA Platforms

While mRNA technology has had great advances, there is still a lot that is unknown about this type of vaccine, including what type of RNA to use and what long-term immune response durability may be.

The continued development of the rapid response platforms is needed to make progress on COVID-19 and future epidemics and pandemics. 

“In all cases, the more robust the platform, in terms of what safety data you have from the platform, what type of immune profile, and importantly, the manufacturing process – which is often really the rate-limiting factor, [the better it is to]…get them as fine-tuned as possible,” said Saville. 

The manufacturing the Pfizer/BioNTech and Moderna vaccines is limited and is largely centered in Europe and North America. 

“What we need to really look at in the medium and longer-term [is]…how can that manufacturing footprint be much more amenable with regional manufacturing capacity,” said Saville. “Looking at manufacturing innovation…that could be amenable to the low- and middle-income countries [is] something that really needs to be followed.”

Innovations in Manufacturing

While numerous accomplishments have emerged from the COVID-19 pandemic, several shortcomings, particularly in vaccine development and manufacturing, have occurred.

“There’s no question that COVID has demonstrated the potential of vaccine development and R&D, but it has also exposed some pretty major gaps in the system and [has shown] what happens when a disease strikes the entire world at the same time,” said Selwyn. 

These gaps include the limitedd supply of vaccines secured for low- and middle-income countries; high-income countries pre-ordering large amounts of vaccines for themselves; the reduction in production capacity for other diseases, which may increase the risk of outbreaks; and the dependency on tech transfers. 

“In COVID, there were multiple companies who had quite limited experience with vaccine manufacturing and bringing vaccines through licensure, [who were] planning for upwards of 10 tech transfers in a single year,” said Casey Selwyn, senior officer in Vaccine Development and Global Health COVID-19 Response at the Gates Foundation, at a workshop that followed the opening session. Normally a company may undertake one transfer a year.

“To maximize global supply, we need to have innovative ways to ease and encourage tech transfer…A tech transfer requires time, it requires resources and sharing of know-how, not just intellectual property,” Selwyn added.

The most efficient way to scale up vaccine production and supply over the long term is to build “ever-warm” vaccine facilities that are multi-platform and multi-purpose with a trained workforce, so that the facilities can be prepared when an outbreak occurs, proposed Selwyn.

Another recommendation for innovating global manufacturing was to implement a hub and spoke distribution model, which would create a centralized network where products are received in central locations before being sent directly to their destinations. 

According to Selwyn, this could ease the pressure of tech transfers and establish a better geographical reach, creating a more flexible, accessible and cost effective system.

Alternatively, increasing standardization of manufacturing protocols and regulatory requirements – which could include the labeling of products, serialization, and design of protocols – could also improve speed, flexibility, and cost-efficiency. 

“Probably one of the most important sets of innovations, sets of lessons and sets of actions for the future is really continuing to pursue uniformity and harmonization, especially for a set of diseases and pathogens that require rapid response,” said Anant Shah, New Product Lead for Global Vaccines for COVID-19 and Ebola at Merck. 

“We have to pursue uniformity, flexibility and efficiency if we want to continue ensuring global equitable access,” said Shah.

Image Credits: NBC, GVIRF.