Companies at the forefront of coronavirus vaccine research have been a veritable gold mine for investors this year. For example, shares of Moderna (NASDAQ:MRNA) have gained a staggering 278% over the first seven months of 2020, while Novavax's (NASDAQ:NVAX) stock has posted a healthy 3,500% return on investment during this same period. 

Which COVID-19 vaccine play might be the next big winner for early shareholders? While Heat Biologics (NASDAQ:HTBX) and Vaxart (NASDAQ:VXRT) have both made quantum leaps in terms of their market caps this year, there's a strong chance that each of these lesser-known COVID-19 vaccine stocks may soon be gearing up for another jaw-dropping move higher. Here's why. 

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Heat Biologics

Last week, Heat announced that its COVID-19 vaccine candidate passed a crucial proof-of-concept animal study. The big deal is that the pre-clinical data might pave the way for early-stage human trials, along with grant funding in the near future. 

Bears, though, don't seem to be impressed with the pre-clinical data or the company's longer-term prospects as a COVID-19 vaccine player. As proof, Heat's stock has fallen by over 27% since this latest program update only a few days ago.

The short thesis appears to center around the fact that Heat's vaccine candidate has yet to enter human trials. Meanwhile, AstraZeneca, Johnson & Johnson, Moderna, Novavax, and Pfizer are already gearing up to produce their experimental vaccines on a commercial scale. 

Is Heat too late to the party? No, not by a long shot. What the bear thesis is missing is that Heat's COVID-19 vaccine is designed specifically for hard-to-treat patients, such as the elderly or the immunosuppressed. In all likelihood, the first cohort of approved COVID-19 vaccines won't provide adequate immune protection for these high-risk groups. Heat is thus attempting to fill a major gap in the battle against COVID-19.

The bottom line is that Heat's unique angle should allow it to land a sizable grant soon, despite its latecomer status. Underscoring this point, Heat confirmed via email last week that discussions with state and federal government agencies about funding are indeed taking place.

That said, this small-cap biotech stock is still an ultra-risky growth vehicle. Government funding is far from a sure thing, and there's no guarantee that these pre-clinical results will hold up in human trials. As such, this speculative coronavirus stock is arguably only suited for investors comfortable with risk.  

Vaxart 

Like Heat, Vaxart is pursuing a novel COVID-19 vaccine candidate -- namely, an orally administered vaccine. The company hasn't yet snagged any major grants to ramp up the development of its oral vaccine. But Vaxart's COVID-19 vaccine candidate was included in a primate challenge by the U.S. government's Operation Warp Speed program last June. So there's no doubt that the biotech's vaccine candidate is indeed on the radar of the federal government. 

Why does this matter? Operation Warp Speed kicked off its initial round of funding by focusing on a select group of five candidates with the highest probability of success. But vaccines have an extremely poor track record in the clinic.

What this means is that Operation Warp Speed will more than likely broaden its financial support to include earlier-stage COVID-19 vaccines in the not-so-distant future. That's the prudent course of action based on the history of vaccine development.

Moreover, the U.S. government appears keen to throw billions more at COVID-19 research as part of the next relief package. Vaxart thus stands a better-than-average shot at hauling in an enormous grant, perhaps within a few weeks' time.

On the flip side, Vaxart is on the spicy side of things from a risk standpoint. A clinical setback would certainly cause this stock to lose a significant amount of value in the blink of an eye. That's important to keep in mind. Vaxart's stock does have tremendous upside potential, but its downside risk shouldn't be brushed off lightly, either. 

This article represents the opinion of the writer, who may disagree with the “official” recommendation position of a Motley Fool premium advisory service. We’re motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.