鶹ý

Is the Novavax COVID Vaccine Worth the Hype?

— The technology is quite innovative and has potential to enhance protection against SARS-CoV-2

MedpageToday
A photo of a healthcare worker holding a box of Nuvaxovid in her white rubber gloved hand.

The favorable analysis of Novavax's COVID-19 vaccine by an FDA advisory committee means the U.S. is likely to soon have a fourth COVID-19 vaccine available for adults, pending any delays.

But with COVID-19 vaccines already widely available, and most adults who will get vaccinated already having done so, why should we care?

Unpacking Traditional

One of the many buzzwords that surround Novavax's vaccine, which has been available in the E.U. for some time, is "traditional." However, it is important to understand this concept and how truly innovative this vaccine is.

From a practical standpoint, the vaccine is easier to handle and doesn't require the of the current mRNA vaccines. This will make the vaccine logistics easier and more efficient.

What about its constituents? The Novavax vaccine is protein-based. It delivers the SARS-CoV-2 spike protein (the antigen) in the injection while the mRNA and viral vector vaccines deliver the genetic sequence of the spike protein to the body's cells, which then manufacture the spike protein. This type of antigen delivery is very familiar and characterizes the nature of several other vaccines, notably the injectable influenza vaccine.

But the Novavax vaccine is innovative in its own right even though its end result is a standard protein vaccine. What is most innovative is that the protein is produced using a platform technology that employs insect cell lines and insect viruses. In a process like that used in the FluBlok influenza vaccine, the spike protein is inserted into a baculovirus (a virus that infects insects), which is then used to infect insect cells that pump out the spike protein used in the vaccine. This cell line, known as a baculovirus expression system (BEVS), is very versatile and an important aspect of vaccine technology.

The Novavax vaccine is coupled to an adjuvant. Adjuvants are substances used to boost immune responses. For example, the standard Tdap vaccine includes aluminum as an adjuvant. Novavax's adjuvant is called Matrix-M and is derived from a family of molecules known as saponins, which originate in the soap box tree. A similar adjuvant is included in the Shingrix shingles vaccine.

Now, on to Novavax's real life application: the question at hand is whether the vaccine will help protect more adults against COVID-19.

The Vaccine Hesitant

Currently, approximately are not fully vaccinated against COVID-19, and a portion of these adults are considered vaccine hesitant. Some people believe a vaccine such as Novavax's may be more palatable to this segment of the population because of how the mRNA and viral vector vaccines have been unjustly maligned.

However, at this point in the pandemic, I do not expect to see much uptake of this vaccine by those who have refrained from getting vaccinated. Recall the widely held notion that a proportion of this segment was supposedly awaiting full FDA approval to get vaccinated -- yet, no major jump in vaccination rates were seen when Pfizer and Moderna both were granted full approval. While we can be hopeful for uptake of the vaccine, we should also be realistic. Just look at the where the vaccine has been available for several months and there has been no surge in uptake. In my mind, the vaccine hesitant adults that remain are unlikely to change their minds (though some may continue to try, and other tools such as antivirals and monoclonal antibodies can be lifesaving for them). It is the scientific method that they must come to accept before they will accept any specific vaccine. After all, it is the same scientific method that generated the prior COVID-19 vaccines as generated this one and will generate all future COVID-19 vaccines and other vaccines.

A potential important caveat is that perhaps if pediatric indications for the vaccine are pursed, this vaccine might be a more acceptable vaccine to parents who have refrained from vaccinating their children with the Pfizer vaccine. However, it would have to first be proven safe and effective in this population, and closely examined for increased incidence of myocarditis, as we've seen in adults.

Mixing and Matching Boosters

An additional benefit of Novavax is having a vaccine using a disparate technology to potentially enhance future mixing-matching booster strategies for the vaccinated. It is that different presentations of the spike protein to the immune system may produce extra benefit compared to repeatedly boosting with the same product. As we optimize booster strategies, having as many components as possible to mix-and-match to find the best durability and breadth of response against variants will be key. Within the scientific community, we are keenly awaiting results of studies using the Novavax vaccine as a booster for those who have received their primary series using other technologies.

The most remarkable aspect of the Novavax vaccine's impending availability is more overarching. The fact that we will have four vaccines -- not to mention many more outside the U.S. -- against a pathogen that, until December 2019, was not even known to science is a testament to the power of a concerted effort of powerful scientific minds to wield incredible tools to successfully solve a complex life-or-death problem.

is a senior scholar at the Johns Hopkins Center for Health Security and a practicing infectious disease, critical care, and emergency physician in Pittsburgh. He has no relevant disclosures.