With 13 COVID-19 vaccines in use worldwide, pharmaceutical companies are exploring second-generation technologies that can change the way doses are administered and distributed.
These vaccinations can be taken orally as a capsule that can be swallowed, as a tablet that dissolves under the tongue or as a nasal spray. Such formulations do not require refrigeration, nor do health professionals need to administer them.
The efforts are in the early stages without guarantee of success. The cost of research and development is high, and only a small number of companies – of which no medicine currently has a vaccine – are exploring these alternative methods. The work looks like a gamble, but could play a critical role in ending the pandemic.
“It’s encouraging to see manufacturers chasing the formulas for the vaccine that are easier to administer,” said Esther Krofah, executive director of the FasterCures of the Milken Institute. “We need to have a global focus and not just a domestic focus.”
With 22% of the population fully vaccinated, the United States administered more doses than any other country in the world, and the data show that high-income countries distributed doses more effectively than low-income countries.
“The United States cannot be safe if the rest of the world is not safe,” he said. Bruce Innis told PATH, a non-profit organization operating in 70 countries to ensure global healthcare. “In a time in the country where the lens is applied to everything, we can not feel good about getting a vaccine if it does not happen everywhere.”
Current vaccines require syringes and refrigeration. These requirements present logistical challenges if the SARS-CoV-2 virus is to be eradicated.
The Moderna and Pfizer vaccines require ultra-cold storage or dry ice. The Johnson & Johnson vaccine, which was suspended while officials studied reports of very rare but dangerous blood clots, could be stored in temperatures just above freezing.
According to FasterCures, which follows 326 COVID-19 treatments and 252 vaccines, five companies are developing oral vaccines, and two – ImmunityBio and Vaxart – have progressed to Phase 1 clinical trials.
Thirteen companies are working on intranasal sprays, and five are in early clinical trials.
“We should not underestimate how challenging it is to create the right vaccine formulations that will generate an effective immune response,” Krofah said.
Dr William Schaffner, an expert in infectious diseases at Vanderbilt University and the medical director of the National Foundation for Infectious Diseases, said he was under the impression that two businesses were in Phase 1 trials.
“People have been looking for an oral vaccine for a long time without much success,” Schaffner said. “It’s exciting, new and distinctive.”
Other experts follow a wait-and-see approach.
“Phase 1 is a long, long way to have a product,” said Dr. Paul Offit, with the Children’s Hospital of Philadelphia, said in an email, adding that the U.S. Food and Drug Administration has no disadvantage in approving early studies.
“I will pay attention when it goes from phase 1 to phase 2 and to phase 3,” said dr. Kelly Moore, deputy director of the Immunization Action Coalition, a non-profit organization that provides information on vaccines and their distribution, said. “Many good ideas fall out between phase 1 and phase 2, and even more do not reach it in phase 3.”
In February, the FDA approved the extension of a Phase 1 clinical trial by ImmunityBio to include two other versions of its COVID-19 vaccine: a capsule that can be swallowed and a tablet that dissolves under the tongue. The company has been testing the injectable version of its vaccine for six months. The tests are applied by Hoag Hospital Newport Beach and have expanded from 35 to 140 participants.
ImmunityBio, based in El Segundo, is the only company testing both injectable and oral versions of its vaccine at the same time, according to FasterCures data. ImmunityBio’s chairman and CEO, dr. Patrick Soon-Shiong, also owns the Los Angeles Times.
The vaccine developed by ImmunityBio differs from the vaccines developed by Moderna, Pfizer and Johnson & Johnson. These vaccines stimulate the immune system to form antibodies against the protein of the virus. However, the immunityBio vaccine is designed to produce antibodies against not only the protein on the outside of the virus but also another protein in the virus.
Because the protein inside is less likely to mutate than the protein, the vaccine may be more effective against coronavirus variants, experts say.
“My concept of an ideal vaccine,” Soon-Shiong said, “is one that does not require refrigeration, and offers quadruple immunity with antibody, T cell, mucosal and long-term memory protection, and most importantly, it protects against the variants that are now emerging. ”
Last week, ImmunityBio announced preliminary results of the Phase 1 trial of its injectable vaccine, which showed a “tenfold increase” in the T cell response – a major immunological response – among trial participants, compared to people who was infected. with the virus.
The biotechnology firm Vaxart, based in southern San Francisco, began Phase 1 clinical trials this fall for an oral COVID-19 vaccine.
Preliminary results released in February indicated that although our vaccine does not produce neutralizing antibodies, “we have seen fantastic T cell responses,” said Sean Tucker, founder and CEO of Vaxart.
“The profile of a tablet vaccine is compelling,” Tucker said, adding that it is stable at room temperature and the fact that it is easy to transport and swallow and that it is not needles to administer. ‘However, it was just difficult to make oral vaccination work. The vaccine usually expires like food. ”
The oral polio vaccine – a measure of success – took almost ten years to develop. The oral version, formulated by Albert Sabin, was first presented in 1953 by dr. Jonas Salk introduced as an injectable vaccine. The oral version, formulated by Albert Sabin, appeared in 1962. The near extinction of polio around the world is mainly attributed to the ease of an oral vaccination.
But the poliovirus is a different kind of virus than the new coronavirus. Both are equally contagious, but a polio infection begins in the digestive tract before it reaches the nervous system and causes paralysis. An oral polio vaccine is targeted at the initial site of infection.
Oral vaccines were also effective against rotavirus and salmonella, but according to dr. Buddy Creech, director of the vaccine research program at Vanderbilt University Medical Center,’s the challenge is to make sure enough of the vaccine survives in the stomach to trigger immune. reaction.
As a respiratory disease, a coronavirus infection is similar to flu, and although the flu vaccine is usually given as a shot in the arm, one company has developed an intranasal version. FluMist is an aerosolized spray that targets the nose and throat, where the virus’ infection often begins. FluMist, Creech said, delivers an immune response at the same level and in some ways better than an injected vaccine.
Methods of administering a vaccine are not the only obstacle to greater distribution worldwide. The Pfizer and Moderna vaccines should be stored at 94 degrees Fahrenheit, and the Johnson & Johnson vaccine should be stored at 36 to 46 ° F.
According to a company spokesperson, Pfizer is developing a powder version of its vaccine. Essentially lyophilized, a vaccine in this form is more stable than a liquid vaccine, and its storage requirements are comparable to the Johnson & Johnson vaccine.
Once in place, the Pfizer vaccine would be reconstituted as a liquid and injected. It is also reformulated to require one shot. Clinical trials with this version of the company’s injectable vaccine have not yet begun.
Moore, of the Immunization Action Coalition, is a “big investment” in finding an alternative method of delivering vaccines. Therefore, most companies avoid it, and for companies that still need to produce a viable vaccine, it is a gamble.
“Convenience is pointless if the vaccine does not work,” said Dr. Lawrence Steinman, an immunologist and neurologist at Stanford University, said.