Does convalescent plasma therapy work? Is a successful vaccine for COVID-19 on the way? Will it be suitable for senior citizens and available to minority communities that were hardest hit by the pandemic? These pressing topics are explored in a recent Aspen Ideas: Health panel discussion that was led by Kenneth L. Davis, MD, President and Chief Executive Officer of the Mount Sinai Health System. Mount Sinai’s renowned vaccinologist Florian Krammer, PhD, and infectious disease specialist, Judith A. Aberg, MD, weigh in with informative answers to some of the nation’s most important health care questions.

“Many vaccine trials fail,” says Dr. Krammer, “but if you go with diverse approaches to creating a vaccine, it is very likely that one or even more of these will succeed.” With regard to convalescent plasma therapy, Dr. Aberg says, timing is everything. Administer the treatment early on before patients develop their own antibodies. Mount Sinai, she adds, is educating at-risk communities about the need for COVID-19 vaccines. When vaccines are ready to be administered Mount Sinai will be there.

To learn more about the most promising vaccines under development, why the infection rate in New York City is relatively low at this time, and whether we should be concerned about mutations to the SARS-CoV-2 virus, go to Aspen Idea’s Perspectives in Health.

Florian Krammer, PhD

As the SARS-CoV-2 virus circulates throughout the world unchecked, researchers are racing to develop more than 135 vaccines. How well will these vaccines work and how soon will we be able to benefit from them? To answer these questions and more, Mount Sinai Today turned to a leader in SARS-CoV-2 antibody research, Florian Krammer, PhD, Mount Sinai Professor in Vaccinology at the Icahn School of Medicine at Mount Sinai. Dr. Krammer is an experienced virologist whose Mount Sinai lab is working on a universal flu vaccine.

What does the vaccine landscape look like?

Vaccines have been made in record time, and they use different platforms. Two candidates use RNA technology, which has never been used in a vaccine before. Typical vaccine development can take up to 15 years but this is now getting shortened to months. Right now, there are more than 20 candidates already in clinical development around the world. Five of these are being developed in the United States. This makes me happy because there is not a single vaccine that can meet the entire demand of the market and if some fail there are alternatives.

Do any of the vaccine candidates look promising?

I am very positive about what we are seeing so far. We’ve seen pretty encouraging results from preclinical models, the phase 1 and phase 2 trials. But none of this means anything yet because the proof will be in the results from the phase 3 trials. That’s where we will learn about the actual efficacy and safety. In terms of efficacy, I don’t think we will end up with a vaccine that gives us 100 percent protection from infection (meaning sterilizing immunity). But we do not need a perfect vaccine, and I am relatively hopeful that several vaccine candidates will lead to solid protection from disease. I think a vaccine will probably also dampen transmission. This will help people who aren’t able to get vaccinated or mount a strong response after they are vaccinated.

When can we expect to see phase 3 trials?

Phase 3 trials are already ongoing. I assume we’ll have pretty good data sets by late fall or early winter, especially from interim analysis of the phase 3 trials. It’s very important that we don’t cut corners in terms of safety or efficacy even if countries like Russia are licensing vaccines right now, and China is giving its vaccine to the military. We really need to see what the phase 3 trials tell us and we need to rely on the U.S. Food and Drug Administration to make a judgment call and only license vaccines that are safe and that work even if they are not perfect in terms of efficacy.

What can go wrong in a phase 3 trial?

If you don’t see efficacy, you don’t go forward. A lot of other things can go wrong. Vaccines can trigger an unintended neurological issue or an autoimmune disease in rare cases. You wouldn’t see this in a few hundred people in phase 1/2 trials, but you would see one, two, or three cases in a few thousand people. An example of this happened in 1976, after an outbreak of swine flu among soldiers at Fort Dix, New Jersey, led to massive vaccination campaigns and increased cases of Guillain-Barré syndrome.

Do we know how the vaccines will work in children or the elderly?

All COVID-19 vaccines tested so far in the clinic show relatively high but acceptable reactogenicity—adverse reactions, including fever and a sore arm at the injection site. Since there is often a lot more reactogenicity in kids than in adults, we need to see if that is also an acceptable level in children. In terms of age de-escalation, I’m not sure what the vaccine producers are planning for phase 3 trials. Typically, you would start testing in healthy young adults and work your way down in age. But if you see a safety signal that’s unacceptable, you may end up with a vaccine that is licensed for adults but not below a certain age group in children. I am not too worried about safety in older people but I am worried about their immune response. We know we have a lot of trouble inducing immune response with flu vaccines in older people and we even have special vaccine formulations for that age group. It’s not clear if we will run into the same problems with COVID-19 vaccines. Some of the phase 3 trials will include people in their 70s, up to 80, so this is something we should know about soon.

What could complicate the rollout of an effective vaccine?

Large-scale production is difficult, and a couple of front runners in this race have never produced a vaccine for the market. A lot of the technologies being used are new and there is little experience with scaling them up. Also, we don’t know who will get the vaccine first. Probably health care workers and high-risk individuals, but I would like to see a discussion about this and understand what the public thinks. Also, distribution and administration of that many vaccine doses needs to be coordinated well and will be a huge effort. You also have to take into account that there will not be instantaneous protection. You may need two shots, and it could take a few weeks to a month until you mount protective immunity. In the United States alone we will need 660 million doses (two shots per person). Globally, we will need 16 billion doses. It’s almost unimaginable how much vaccine we will need.