COVID vaccine updates – large clinical trials will be unnecessary

The questions I keep getting are will we need COVID-19 vaccine updates and how fast could we get them. These are important questions going forward, especially since there are some dangerous variants that seem to be spreading widely.

I think we should look at the model for flu vaccines – each year the antigens are targeted by the vaccine are changed slightly to improve effectiveness. Admittedly, with the flu vaccine, it’s hard to do since the influenza virus can mutate rapidly.

However, regulatory agencies worldwide do not require massive clinical trials for the new formulations, as long as nothing else changes except for the antigens. That’s the model that we will probably require for future COVID-19 vaccine updates in the future.

Why will we need updates or boosters?

This is all about the new variants that are circulating – what is the best way to update the COVID-19 vaccines?

All of the vaccine manufacturers that are currently licensed in the USA, Pfizer, Moderna, and JNJ,

Photo by CDC on Unsplash

COVID vaccine updates – the flu vaccine model

I think there is an impression (trope, myth, meme) that scientists throw darts at a dartboard to determine the antigens for a vaccine. Of course, people are going to wonder the same thing about how we might determine COVID-19 vaccine updates in the future.

The flu vaccine will be a good model on how we get new vaccines.

First, I need to explain how the vaccine actually works. Without getting too complicated, the flu vaccine induces a systemic immune response to a part of the influenza virus called hemagglutinin, which is a glycoprotein found on the surface of influenza viruses. Both inactivated and live influenza vaccines induce virus-specific serum antibodies which can protect against infection with wild influenza virus possessing the same hemagglutinin antigen.

The reason that each flu season brings a new risk for contracting the disease is that the virus has frequent mutations of the hemagglutinin, so the immune system doesn’t recognize the virus anymore, and you contract the flu. It doesn’t matter if you get the flu “naturally” or boost your immune system with a vaccine, you are generally susceptible to the newly mutated flu virus each year.

Of course, this makes it difficult to develop a flu vaccine every year, because national health organizations, like the US Centers for Disease Control and Prevention, have to scientifically predict which mutated viruses might be prevalent in the upcoming flu season. It’s difficult to predict the exact antigen if there are frequent mutations in the flu virus.

Unfortunately, vaccine manufacturers require a six-month lead time prior to shipping the vaccine, scientists must quickly determine what the new mutated types might be.

The first step is that over 100 national influenza centers in 100 countries receive and test virus samples from patients in their countries. These centers then send samples of the most prevalent viruses to five World Health Organization (WHO) Collaborating Centers for Reference and Research on Influenza,  which include the following research organizations:

Twice a year, February for the Northern Hemisphere and September for the Southern Hemisphere, WHO gathers the five Collaborating Centers to meet and discuss which flu virus mutations are going to be prevalent.

The key scientists from each of these centers review the results of surveillance, laboratory, and clinical studies, and the availability of vaccine viruses and make recommendations on the composition of the upcoming season’s influenza vaccine. Generally, the group decides on three subtypes of the flu virus – H1N1 (a subtype of A flu), H3N2 (another subtype of A flu), and type B strains. Recently, a second subtype of the B type virus is included in the quadrivalent flu vaccines.

WHO recommends specific flu strain antigens for inclusion in the vaccines; however, each country reviews the data and may modify the viruses in the vaccines for their own country. For example, in the USA, the Food and Drug Administration (FDA) makes the final decision about vaccine viruses, with input from the CDC, that will be used in vaccines sold in the USA.

The updated vaccines do not require large clinical trials, as they could delay the introduction of a new influenza vaccine by months or years – thus, the FDA and other regulatory agencies, like the European Medicines Agency (EMA) only require the vaccine manufacturer to determine that its vaccine is effective by showing that it induces antibodies in a few hundred patients. The vaccine must not have any other changes, except for the antigens.

If a new vaccine is introduced, with a whole new formulation, regulatory agencies require a new drug application which will require years of preclinical and clinical trials.

FDA guidance

According to new guidance from the FDA on COVID-19 vaccine updates, they state:

The updated guidance outlines the FDA’s scientific recommendations for modifications to authorized vaccines. For example, the FDA expects that manufacturing information will remain generally the same for an authorized vaccine and a modified vaccine candidate from the same manufacturer. For clinical data, the guidance recommends that a determination of effectiveness be supported by data from clinical immunogenicity studies, which would compare a recipient’s immune response to virus variants induced by the modified vaccine against the immune response to the authorized vaccine. Manufacturers are also encouraged to study the modified vaccine in both naïve (non-vaccinated) individuals and in individuals previously vaccinated with the authorized vaccine. Additionally, the guidance outlines the FDA’s recommendations for assessments of safety to support an EUA for a modified vaccine. Finally, the guidance states that further discussions will be necessary to decide whether in the future, modified COVID-19 vaccines may be authorized without the need for clinical studies. 

What does this mean? Any adjustments developers make for new variants would need small trials, like those required for annual flu vaccines.

Citations


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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!