Over the last 18 months, COVID-19 has dominated the stock market in general, and vaccine stocks in particular. Companies and governments are trying to vaccinate as many people as possible to minimize the threat of this disease and maybe even eradicate it. That's the here and now, and any news can send vaccine stocks soaring, or crashing, overnight.

It's hard to imagine what the vaccine stocks will look like 10 years from now. Will COVID-19 still be in the headlines? Or will it recede in importance? A group of Fool contributors suggest you might want to buy shares of Moderna (MRNA -0.74%), Pfizer (PFE), and Vir Biotechnology (VIR 2.12%). Here's why. 

A patient receives a vaccination.

Image source: Getty Images.

This vaccine superstar will continue to outperform

Patrick Bafuma (Moderna): Talk about setting a high bar with your first drug to market. With $20 billion in advance purchase agreements for 2021, Moderna's COVID-19 vaccine, Spikevax, is set to rival Humira for the best-selling drug in the world in 2021. Not to be proved a fluke, in 2022 this vaccine giant also has $12 billion in advance purchase agreements and another $8 billion in options for Spikevax.

If there is one thing COVID-19 has demonstrated, it is that this disease is resilient. With New York City set to implement vaccine passports for gyms and indoor dining, other destinations may not be far behind. And with some employers and higher education programs starting to require vaccinations, not to mention the inevitable need for boosters, I believe the demand for jabs of the company's product, which just generated $4.4 billion in second-quarter revenue, will likely remain high.

We already knew the COVID-19 vaccine was a boon for Moderna. And its flu vaccine is expected to be on the market in 2023 -- a market worth $5 billion to $6 billion annually. And you probably already knew that the mRNA specialist was working toward having a combination flu/respiratory syncytial virus/COVID-19 vaccination. Maybe you even knew that the company's $2 billion to $5 billion cytomegalovirus vaccine candidate is close to entering phase 3 trials. What you may not have known about is CEO Stéphane Bancel's long-term investment in oncology vaccines.

The company has two exciting cancer vaccines in a 50-50 partnership with Merck (MRK 0.81%) that I am keeping an eye on. These vaccines work by providing patients with an injection of mRNA that gets the patient's immune system to recognize specific abnormalities that are the hallmark of cancerous cells and then get the patient's own immune system to attack the cancer.

The most advanced product of this collaboration, a "personal cancer vaccine" for head and neck squamous cell carcinoma, is currently in phase 2 trials. Thus far in its earlier trials, the treatment has a 50% response rate, more improvements in tumor burden over time, and longer progression-free survival than current standards of care.

The other Merck-partnered oncology vaccine, while only in phase 1 trials, has a massive addressable market. This one targets mutations within the KRAS gene, with alterations of KRAS present in more than 20% of human cancers. With Moderna's KRAS vaccine covering 80% to 90% of KRAS mutations with its vaccine, this has potential to be another multi-billion-dollar treatment for the company.

Yes, Spikevax will continue to be the company's cash cow. However, with $12.2 billion in cash and investments, and generating over $4 billion in revenue a quarter, the company has plenty of cash to fuel its research and development pipeline. If we're looking for an innovative vaccine maker to boost the portfolio of healthcare investors for the next 10 years, Moderna has lots of firepower in its pipeline, street credibility, and plenty of cash to make it all happen.

A $7-billion-a-year opportunity

George Budwell (Pfizer): Although vaccines have long been a steady source of revenue for multiple big pharmas, investors have historically ignored the value of this particular product category -- that is, until the COVID-19 pandemic hit. The core reason is that vaccines, by and large, tend to be modest revenue generators for their manufacturers, with a few glaring exceptions such as GlaxoSmithKline's Shingrix and Pfizer's blockbuster Prevnar franchise.

Another issue is that vaccines have proven to be extremely difficult to develop for some of the most common viral agents. Respiratory syncytial virus, for example, is a seasonal illness that reportedly results in a whopping 58,000 hospitalizations per year in children younger than 5 and 177,000 in people over the age of 65, according to the Centers for Disease Control and Prevention. Yet there are still no fully protective vaccines approved for this large unmet medical need -- despite multiple attempts to develop such a vaccine over the past 60-plus years. Wall Street analysts, in turn, believe that the first company to achieve this lofty goal could be awarded with a product capable of generating over $7 billion per year in sales.

Which big pharma has the inside track at breaking into this enormous market? As things stand right now, Pfizer is arguably sitting in the catbird seat with its RSV candidate known as RSVpreF. The company recently rolled out exceedingly impressive results for the vaccine in a midstage challenge study in adults under the age of 50. Pfizer has thus decided to advance RSVpreF into a critical phase 3 trial in adults, which is set to kick off next month. Top-line results from this global phase 3 trial ought to be available sometime in the first quarter of 2022.  

If this highly anticipated trial does indeed hit the mark, the pharma titan would almost certainly have its next superstar vaccine product -- possibly making its stock a great buy for long-term investors. 

"A world without infectious disease"

Taylor Carmichael (Vir Biotechnology): Vir Bio's mission statement -- "creating a world without infectious disease" -- is kind of amazing. If the biotech succeeds in eliminating infectious disease from the planet, it will be the most valuable healthcare company in the world.

While it's hugely ambitious, it's not impossible. After all, we've largely eliminated some viral diseases like polio and smallpox. And it was vaccines that did it. What Vir is attempting to do, as I understand it, is use the breakthroughs in genomic research to find one-and-done vaccines for diseases like COVID-19, hepatitis B, influenza, and HIV. The company actually has four platforms, focused on antibodies, T cells, innate immunity, and small interfering ribonucleic acid (siRNA). 

We might ask why this vaccine company isn't a leader in COVID-19 vaccines. Vir Bio may or may not be in last place, but it's way back in the race. The company's vaccine, sotrovimab, is still in its pre-clinical phase. Meanwhile, the mRNA vaccines from Moderna and BioNTech have been on the market for months. The Novavax vaccine has suffered delays, but should be on the market soon. This is a remarkably quick pace, and shareholders of all three companies have been amply rewarded over the last 18 months.

NVAX Chart

NVAX data by YCharts

Compared to the 5,000% return of Novavax, or the 2,000% return of Moderna, or the 1,000% jump BioNTech investors have received, Vir's 200% gain is a little disappointing. (On the other hand, Vir shareholders did six times better than people who invested in an index fund.) 

The main reason Novavax, Moderna, and BioNTech have soared is that all three companies focused on the spike protein of the coronavirus. This has been incredibly successful, creating large numbers of antibodies. If a vaccine produces a large enough level of antibodies, it wards off the disease and keeps people from getting infected.

What about the future, and all the mutating strains? Historically, the way vaccine companies dealt with mutation in the past, like with the flu, was to vaccinate people again and again. You vaccinate for the known strains and hope the drug will produce enough antibodies and T cells to ward off mutating strains as well. That's why both Novavax and Moderna are pursuing a flu/COVID-19 combo shot -- the plan is for people to take it every year.

That plan might come to a crashing halt if Vir succeeds with its one-and-done vaccine. While Vir might seem too far back in the race to make any difference, the company has an ace up its sleeve. The Food and Drug Administration has given the company an Emergency Use Authorization to market sotrovimab not as a vaccine, but as a treatment for people who have already been infected with COVID-19. So investors will have real-world data about how the company's drug works.

Of course the COVID-19 treatment market is vastly smaller than the vaccine market. But what makes Vir so interesting is the company's ultimate focus. Its mission is to eliminate infectious disease from the planet. Today, you might invest in Vir for its COVID-19 treatment. But what's really exciting are the vaccines the company hopes to introduce over the next decade. If Vir successfully removes one major illness from the world, investors will make a lot of money.