Charting the Future of Vaccines

The arrival of the first messenger RNA (mRNA) vaccines to the market ushered in pharma’s honeymoon period with the technology. After more than 50 years of research (1) into the technology, the ongoing COVID-19 crisis allowed the vaccines to immediately prove their effectiveness on the global stage. Consequently, a veritable gold rush has kicked off, as companies such as Moderna, Pfizer, and Sanofi have begun clinical trials for various types of mRNA vaccines. Moderna, in particular, is evaluating the clinical potential of mRNA vaccines for myriad conditions, including influenza, Zika virus, respiratory syncytial virus, human immunodeficiency virus (HIV), cytomegalovirus, and even cancer (2).

However, as the luster of mRNA vaccines shines brighter than ever before, it is worth considering how these products factor into the greater vaccine marketplace. This article will unpack the unique attributes of mRNA vaccines, how they compare to traditional alternatives, and what use cases they are suited for.

The appeal of mRNA

At a basic level, mRNA vaccines function by inserting an mRNA strand that corresponds to a viral protein, allowing cells to produce viral proteins and produce antibodies. This is not dramatically different from how conventional vaccines work (i.e., by inserting a scientifically weakened version of the virus as an antigen into the body), in principle, but in practice there are a few key differences that made mRNA vaccines invaluable in the fight against COVID-19.

Chief among these differences is the speed of development and delivery. Traditional vaccines need to be grown and cultivated in vessels such as chicken eggs or mammalian cells, and this process of collecting the virus can take months. Conversely, according to a Pfizer informational page, it takes approximately one week to develop an experimental batch of an mRNA vaccine, greatly accelerating time-to-test. In a similar vein, the delivery process can be simplified and accelerated because DNA can be synthesized from a digital sequence (3).

In this regard, mRNA vaccines simplify aspects of the vaccine production process that enable greater flexibility and adaptability. Jeff Fischer, president and co-founder of Longhorn Vaccines & Diagnostics, discussed the merits of this process at length in an episode of Pharmaceutical Technology®’s Drug Solutions Podcast (4). While broader use cases exist, Fischer honed in on mRNA vaccines as particularly useful in the use of personalized vaccines, like those being developed for cancer, because of their quick development time and highly flexible nature.

“I think that the mRNA vaccines [are] going to have a lot of applicability in cancer, in some areas where you’re not necessarily looking for long term [durability],” said Fischer. “And in the case of Moderna, working with Merck, where you’re adding it with a drug, and you’re allowing the vaccine to do
part of the work and you’re allowing the drugs to do the other part of the work, I think that there’s going to be a real focus there.”

The bigger vaccine picture

However, while the benefits of mRNA vaccines have been proven, there are relevant questions concerning ideal use cases because of questionable durability response. Because of the relative novelty of mRNA vaccines, there is a lack of detailed scientific data on the issue. However, what has been observed may deflate some who view mRNA vaccines as a wonder drug.

FDA approval of various booster doses is contingent on clinical trial data that demonstrate significantly increased immune response. For instance, Moderna’s COVID-19 Omicron variant-containing bivalent booster candidate achieved approval when data showed that it exhibited an eight-fold boost in neutralizing geometric mean titers against omicron among
seronegative participants (5).

However, while initial effectiveness is not in dispute, later studies have shown a lack of durable response in mRNA booster vaccines. For example, one study found that, while boosters—in this case, the third and fourth booster shots for both the Pfizer-BioNTech and Moderna COVID-19 vaccines—did demonstrably increase antibody titers following the initial two-dose vaccination, “only 45% to 65% of participants demonstrated a detectable nAb [neutralizing antibody] titer against the newer variants after the booster (third dose)” (6). The study also showed that the immune response declined to below the detection limit in almost all individuals by six months. The study thus concluded that the durability of serum antibody responses only improved marginally following booster vaccines (6). A similar study recommended the use of boosters six-to-eight months after vaccination (7), which is similar to how booster vaccine roll-out ultimately occurred.

“I think that the industry was a little bit surprised by the lack of durability of the mRNA vaccines; I don’t think they could have predicted that,” said Fischer in the podcast interview. “I think there was a rush to now throw everything into the mRNA bucket. And then the same thing was true, I think of the adenovirus-based vaccines: there were some good things seen at small scale, but when you took them up to [significantly] large populations, then you started to see some safety issues that now are putting adenovirus-based vaccines into a black box.”

To many, this degraded response may seem self-evident—even accounting for the existence of variants and mutations to the original virus strain, the need for booster vaccines in and of itself implies some degree of degraded response. However, even if the initial immunization response persists in some form or fashion, a degraded response to vaccines that are not typically administered on a year-to-year basis would not be optimal for many conditions.

One-and-done vaccines, such as those for polio and measles, have significantly higher odds of reaching those who are vaccine hesitant or simply too busy to continue receiving vaccines. The Centers for Disease Control and Prevention currently estimates that while approximately 270 million Americans, or 81.4%, have received at least one dose of a COVID-19 vaccine, the amount who have received the most recent updated bivalent vaccines is approximately 56 million, or just 17% (8). And while COVID-19 vaccines have been shown to remain effective against severe infection even without boosters (6), the underlying technology may not be suitable for diseases where infection must be avoided.

While mRNA vaccines are a proven breakthrough, until the concerns surrounding durable response can be definitively answered, their use case must be narrowed to conditions where a diluted infection is an acceptable outcome, such as yearly influenza, or where the goal is complementary treatment, such as personalized cancer vaccines. While this may fall well short of the “wonder drug” status many are keen to assign these products, mRNA vaccines nonetheless seem poised to transform a significant pharma market segment.

References

1. National Institutes of Health. Decades in the Making: mRNA COVID-19 Vaccines. covid19.nih.gov, Jan. 10, 2023.

2. Billingsly, A. More Than COVID-19: 6 Other Promising mRNA Vaccines in the Pipeline. GoodRx Health, June 16, 2023.

3. Pfizer Staff. What Makes an RNA Vaccine Different from a Conventional Vaccine? Pfizer, May 5, 2020.

4. Playter, G. Drug Solutions Podcast: Evaluating the Vaccine Marketplace.
PharmTech.com, July 18, 2023.

5. Moderna. Moderna Announces Omicron-Containing Bivalent Booster Candidate mRNA-1273.214 Demonstrates Superior Antibody Response Against Omicron. Press Release, June 8, 2022.

6. Arunachalam, P. S.; Lai. L.; Samaha, H.; et al. Durability of Immune Responses to mRNA Booster Vaccination Against COVID-19. J Clin Invest. 2023, 133 (10) DOI: 10.1172/JCI167955.

7. Korosec, C. S.; Farhang-Sardroodi, S.; Dick, D. W.; et al. Long-term Durability of Immune Responses to the BNT162b2 and mRNA-1273 Vaccines Based on Dosage, Age and Sex. Sci Rep. 2022, 2 (1), 21232. DOI: 10.1038/s41598-022-25134-0

8. Centers for Disease Control and Prevention. COVID Data Tracker. covid.cdc.gov/covid-data-tracker, accessed July 11, 2023.

About the author

Grant Playter is associate editor for Pharmaceutical Technology.

Article details

Pharmaceutical Technology
Vol. 47, No. 8
August 2023
Page: 26-27

Citation

When referring to this article, please cite it as Playter, G. Charting the Future of Vaccines. Pharmaceutical Technology 2023 47 (8).