COVID-19 vaccine may be available next year, but 'herd immunity' will still take time

Anthony Fauci, a leading American infectious disease expert, has said that a COVID-19 vaccine could be available within 12 to 18 months. This timeline is not only ambitious but also implies that vaccine development will proceed at an unprecedented pace—typically, a vaccine takes years of testing from development to market.

The challenges are numerous. A vaccine developed so quickly is likely to lack solid data proving its safety and efficacy in preventing infection, which will force regulators to make difficult choices. As of May 4, the global number of confirmed COVID-19 infections exceeded 3.4 million, and vaccine production for the public must proceed at a speed and scale far beyond previous norms. Furthermore, there is no guarantee that a vaccine will provide the broad protection needed to curb the pandemic.

Walter Orenstein, a professor at Emory University School of Medicine and associate director of the Emory Vaccine Center, said in an interview with BioPharma Dive: "I think the 12 to 18 months mentioned is optimistic. If everything goes well, it's possible, but for most vaccines, it takes longer."

The Trump administration's "Operation Warp Speed" has further heightened the urgency of clinical development. The program aims not only to obtain an approved vaccine but also to have enough doses for every American by January next year. The president has demanded that the industry compress a development cycle that can sometimes take decades into just 12 months—a feat that would require the American public to accept higher-than-usual safety risks and the possibility that the first vaccines may not be highly effective.

Protecting the population

Herd immunity refers to when enough people in a population have immunity to an infectious disease, thereby preventing its spread.

Achieving herd immunity to SARS-CoV-2 infection could be the biggest step toward restoring social and economic activity to normal, because if the virus continues to spread and people continue to get sick and die, social distancing measures may remain in place. Economic forecasters' assumptions about future recovery depend on this outcome.

Typically, herd immunity cannot be achieved within one or two years. A vaccine's approval based on its ability to prevent disease in tens of thousands of people can take up to a decade or more. For example, GlaxoSmithKline's vaccine Shingrix was approved based on a four-year follow-up of nearly 33,000 patients, in which the vaccine reduced cases of shingles by about 97% compared with placebo.

However, given the urgency of the COVID-19 pandemic, the U.S. Food and Drug Administration (FDA) may accelerate the standard process and grant an emergency use authorization for a vaccine—a limited declaration that, while not equivalent to standard drug approval, makes a drug available during a public health emergency. This decision could be made even if a vaccine has only shown the ability to induce an immune response in a relatively small population, rather than safely preventing infection.

In such a scenario, public health officials would prioritize vaccinating high-risk groups, such as healthcare workers, with the first batches of vaccine, who in turn would become test cases to determine how well the vaccine actually protects people from COVID-19.

Paul Offit, director of the Vaccine Education Center at Children's Hospital of Philadelphia, said in an interview: "We will learn as we go. When a vaccine has been given to tens of thousands or hundreds of thousands of people, you can really see how effective and safe it is."

But initially, only eligible high-risk groups would be protected. Conducting a mass immunization campaign covering 70% to 85% of the population—the threshold needed to curb the spread of SARS-CoV-2—could take years.

Scaling up production

To achieve mass immunization, the biopharmaceutical industry must overcome several difficult hurdles.

These include: proving that the coronavirus's signature "spike" protein is the correct target; that vaccines training the body to recognize this protein can elicit a deep and lasting immune response without causing other health problems; that companies can meet the enormous demand for an effective vaccine; and that the healthcare system can then carry out a large-scale vaccination campaign.

SVB Leerink analyst Jeffrey Porges recently wrote that, therefore, a two- to three-year timeline is a more realistic estimate for a vaccine to be widely available to the public. He noted that accessibility is only the first step.

Porges wrote in an April 21 note to clients: "In the unlikely event that an approved, effective, and safe universal vaccine is available a year from now, it would still take years to confer sufficient 'herd immunity' to stop endemic transmission of COVID-19. We believe it may not be until 2023 or 2024 that herd immunity sufficient to stop epidemic transmission can be achieved."

Biotechnology and pharmaceutical companies say they are preparing for the daunting production task, getting ahead of the curve among the roughly 100 projects already launched in case a viable candidate emerges. Companies of all sizes are risking capital to produce large quantities of vaccine doses before clinical trials are completed.

For example, Pfizer ispreparing to produce soonmillions of doses of an experimental vaccine developed by its German biotech partner BioNTech, and could produce hundreds of millions of doses next year.

Meanwhile, Johnson & Johnson haspartnered with Catalent, planning to achieve 24/7 production of its candidate vaccine by January 2021. And Moderna, the first U.S. biotech to enter human testing, is using part of the$483 million awarded to itby the U.S. government to book Lonza to produce up to1 billion dosesof its candidate vaccine per year.

However, these investments do not necessarily guarantee that companies can produce at the scale and timeline needed for the pandemic response.

George Benjamin, executive director of the American Public Health Association, said: "If there are production delays, it will look like testing." He was referring to the delayed rollout of SARS-CoV-2 diagnostic tests. "I think the limiting factor will be vaccine supply."

Beyond that, Benjamin said he believes the healthcare system has the capacity to handle a mass vaccination campaign. If needed, healthcare workers could be redeployed from other activities to increase the number of vaccinations. Drive-through vaccinations could ease pressure on clinic space.

A second potential issue is the need for booster shots. Researchers do not yet know whether a single vaccination will confer permanent immunity like the chickenpox vaccine. COVID-19 may require two or more doses, which could lead to additional shortages related to demand.

However, given the limited current understanding of the coronavirus, Offit offers some hope. He said: "At most every few years, assuming the virus is still around. This is not the flu. This virus does not mutate every year. It is a stable virus."

Biological unknowns

Porges's criticism of the rapid timeline promised by Fauci (director of the U.S. National Institute of Allergy and Infectious Diseases) stems from past failures in the biopharmaceutical industry. No company has yet developed an effective vaccine against any coronavirus, and the industry has performed poorly against several respiratory diseases.

Researchers also do not know everything about the coronavirus or the human response to infection.

Orenstein said: "At this stage, we do not fully understand what a protective immune response looks like. We think it is immunity to the 'spike' protein, which makes sense, but only through actual clinical trials can we be fully certain that this is the key aspect for developing immunity."

Additionally, Porges wrote, some of the first vaccines to enter human testing—such as Moderna's mRNA-1273 and BioNTech and Pfizer's BNT162—use newer, unproven technologies. These two candidates can be designed and produced faster than traditional vaccines; they teach the body to produce viral proteins, aiming to train the immune system to fight future infection.

When phase 1 data from these two products are released in the coming weeks or months, we may see some signs of progress. The AstraZeneca-Oxford collaboration and China's CanSino Biologics may also release early results soon, both of which are attempting approaches that rely on genetically modified common cold viruses.

However, if immune responses are seen, how much protection can they provide to patients? Porges has low expectations. He believes the first vaccines may be "prototypes" that will give rise to improved second- and third-generation products, thereby providing herd immunity.

Offit said that ideally, a COVID-19 vaccine should prevent infection in 70% to 80% of those vaccinated. But in other infectious diseases, lower thresholds have also been beneficial. "The current flu vaccine is 50% effective," he said, "but the flu virus kills 40,000 to 50,000 people in the U.S. each year, so even 50% effectiveness has value."

Orenstein also suggested a similar threshold. "Any vaccine with reasonable effectiveness—say 50% or higher—would be beneficial, and many people might consider lower acceptable."

Of course, the size of the vaccine's benefit also depends on how many people get vaccinated. Some in the U.S. have refused vaccines supported by decades of evidence. How would the public react to a new vaccine without an equivalent track record? Porges noted, for example, that a vaccine with 50% effectiveness, if used by 70% of people, would only confer vaccine-induced immunity on 35% of the population.

However, Orenstein believes the public will be eager to get vaccinated.

He said: "I think demand will be high. The bigger questions will be: how effective are our current candidates; how many doses are needed; how long does immunity last; and how many doses can we produce?"