Coronavirus

Improving Vaccine Efficacy in the Age of COVID-19

In the era of the COVID-19 pandemic, vaccines are at the forefront of the public discourse like never before. Removed from the flashpoints of debate and politicization, though, are the researchers and scientists working every day to make vaccines and pharmaceutical drugs more effective, whether that’s for viruses like COVID-19 and the Delta and Omicron variants or for long-standing diseases like cancer or HIV.

Making vaccines and drugs more effective isn’t a simple task; it involves a great deal of trial and error to even identify potential formulations that could work, let alone optimize them for maximum efficacy. The cost of this process can be immense, but the market value is as well – according to the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), the combined direct, indirect, and induced effects of the biopharmaceutical industry’s total contribution to the world’s GDP is $1,838 billion – just shy of $2 trillion.

That’s exactly what Dr. Larry DeLucas, president of Soluble Biotech and SVP of Operations at Predictive Oncology, is focused on. We sat down with DeLucas to find out more about novel approaches that can boost the efficacy of vaccines and other pharmaceuticals and how they’re already being deployed today.

What goes into vaccine effectiveness?

There are two major considerations when developing a new drug formulation that every researcher needs to keep top of mind, according to DeLucas. These are solubility and stability.

Solubility

The solubility of a pharmaceutical product refers to the dissolution of the protein or peptides in the formulation, which supports bioavailability and homogeneity. This is necessary for a vaccine to be effective at helping a patient to build immunity.

“When you inject something like the COVID-19 vaccine into someone, you need so many milligrams of proteins injected in a small volume for it to work,” DeLucas said. “You need to concentrate the protein while maintaining its solubility. The protein is very highly concentrated as a result.”

Unfortunately, there is one major problem: highly concentrated proteins or peptides tend to aggregate, sticking to themselves in the vaccine solution. Once this happens, it is very difficult to break the protein apart again, which unfortunately means the vaccine won’t elicit the desired immune system response to help the patient build immunity, DeLucas said. 

To solve this problem, manufacturers add one or more additives to the formulation, which are known as excipients. Excipients, which could be sugars, amino acids, or polymers, help ensure the protein stays dissolved uniformly throughout the vaccine or drug. To find the best possible combination of excipients, researchers must engage in a timely and costly process of trial and error, examining each in different concentrations and combinations within their pharmaceutical formulation.

This gives rise to another problem: the protein needed for most of these drug formulations is expensive and hard to come by. Trial and error processes then are extremely costly, requiring companies to dedicate grams of their precious proteins to find the best possible formulation – and that’s before even producing enough to begin pre-clinical trials.

“Companies figure out these combinations by trial and error, but there are literally millions of possible combinations to choose from,” DeLucas said. “It’s time-consuming and expensive. The amount of protein they need for each formulation could be 0.5 grams or more.”

Stability

But once the right concentrations and combinations of excipients have been identified, the job is done, right? Unfortunately, that’s not the case. Adding excipients to a drug formulation can affect the stability of the vaccine or drug, a critical aspect of passing regulatory muster.

Of course, where there are pharmaceuticals, there is the U.S. Food and Drug Administration, which must approve all drugs intended for human or animal consumption after rigorous pre-clinical and clinical trials. As part of these trials, the FDA examines how well the vaccine or drug ages to determine its shelf-life and assign it an expiration date that ensures the safety of patients.

“The FDA typically requires over a year of time showing stability at room temperature,” DeLucas said. “Part of FDA approval means we understand the right conditions that [the pharmaceutical product] must be kept in until used.”

The stability data is evaluated by the FDA in regards to a number of factors that can lead to the expiration of a pharmaceutical product, such as exposure to various temperature levels, humidity, oxygen, and light. This evaluation helps guarantee that patients are getting vaccines or medications that are both effective and safe to use. Improving the solubility and stability of vaccines and pharmaceutical drugs offers a better chance at a prolonged shelf-life and FDA approval.

“You’ve got to figure out the right combination that keeps it soluble and makes it stable,” DeLucas emphasized. “You can’t have it breaking down quickly.”

As a result, sometimes after the immense trial and error to find the right combinations and concentrations of excipients for solubility, the stability of a product is totally disrupted, which means back to the drawing board after hours of wasted effort and milligrams to grams of wasted protein.

How to improve solubility and stability testing

DeLucas and his team at Soluble Biotech have uncovered a novel way for pharmaceutical companies to save all that wasted time, protein, and dollars. The solution, he said, lies in leveraging an advanced neural network and innovative approaches in excipient testing in the laboratory. 

“We miniaturized a process known as Self Interaction Chromatography [to determine the most soluble proteins],” DeLucas said, adding that this process only demands 60 to 70 milligrams of protein, whereas other companies traditionally use between 0.5 and 1 gram per formulation to determine solubility. “Oftentimes you can only produce milligram quantities of a protein, so this solves the problem of protein consumption.”

DeLucas and his team enhance protein solubility with the help of artificial intelligence. After identifying several helpful excipients and their concentrations using the Self Interaction Chromatography system, the solution excipient conditions and measured solubility data are automatically input into a neural network. The algorithm does the rest with a process known as back propagation.

In back propagation, the neural network takes about 5% of the existing data and sets it aside without analyzing. Then, leveraging the remaining data, it weights the different excipients and their concentrations and rapidly runs a series of refinements until it can accurately predict the data is set aside. Over time, the algorithm learns and improves – once it reaches a point where the accuracy of its predictions can no longer improve, it then predicts 4,000 new excipient combinations and concentrations to determine the most soluble formulations for the vaccine or drug. 

DeLucas and his team take the top 25 recommendations the neural network returns and test them for solubility and stability. If the formulations meet the team’s expectations and correlate well to the AI’s predictions, they can move forward into development and pre-clinical trials.

“We take a process that usually takes a year and a gram of protein and do it in 3 to 4 months with milligrams of protein,” DeLucas said. 

AI is the future of drug development

The technology in use by DeLucas and the Soluble Biotech team makes their novel approach to drug discovery even more effective, enabling them to identify without all the trial and error the most soluble drug formulations while keeping a close eye on stability. 

The result is a streamlined drug discovery process that takes less time and money to complete and helps pharmaceutical companies get their vaccines into pre-clinical and clinical trials sooner. It also offers drug manufacturers a greater degree of confidence that their products will survive through clinical trials and attain FDA approval, something that is never guaranteed. 

In the past, companies would have to risk wasted resources and funding just to identify possible drug candidates, many of which would ultimately fail in clinical trials. Today, DeLucas and his team are helping to change that with the support of advanced AI technology.

The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.

In This Story

POAI

Other Topics

BioTech

Predictive Oncology

Predictive Oncology Inc. (POAI) is a knowledge-driven company focused on applying artificial intelligence (AI) to develop personalized cancer therapies, which can lead to more effective treatments and improved patient outcomes.

Read Predictive Oncology's Bio