Global pressure for vaccine: WHO calls for calm

The possibility that the Oxford vaccine will be the first to be available before the end of the year has raised enormous international concern: some countries are seeking privileged access to coronavirus immunization.

World leaders are putting the pedal to the metal, wanting workers to be vaccinated as soon as possible so that they can safely return to work and the economy can revive. The US, UK and China are going at a fast pace in their research, as if in addition to human lives, scientific prestige and supremacy were at stake as Russia itself is demonstrating.

In contrast, the World Health Organization (WHO), recently abandoned by the United States following the order of President Donald Trump, presumes that the race for a vaccine will leave aside the emerging and less developed countries; the organization is trying to appease the times, its executive director Mike Ryan insists that "vaccination against the coronavirus will not begin until the first part of 2021.

In the midst of the summer season, with a series of outbreaks and resurgence of coronaviruses in various parts of the world and in the shadow of more than 18 million infections and nearly 800,000 deaths from coronaviruses, the world is crying out for a vaccine to defeat the infectious pathogen.

In the face of this urgency, there is unusual global pressure for a coronavirus vaccine to be available as soon as possible in record time, as the average production time - of an effective immunization - can take an average of 4 to 5 years, from the phase of its experimentation in a laboratory to its production and marketing by a pharmaceutical company.

A few days ago, the University of Oxford and the Jenner Institute caused a great stir, after sharing with the medical journal The Lancet the results of each of their study phases and corroborating that the ChAdOx1 nCoV-19 vaccine unleashes "a strong" immunity.

"It does so in T cells by provoking a response within 14 days of vaccination (white cells can attack SARS-CoV-2 infected cells) and by generating antibodies within 28 days (antibodies allow the virus to be neutralized so that it cannot infect other cells)," according to the published tests. 

Even the British Prime Minister himself was optimistic on his Twitter account @BorisJohnson, noting that "this is very positive news. How well it has been done for our brilliant scientists and researchers.

The event takes place inside the Jenner Institute, which bears the name of one of the great pioneers of vaccines: Edward Jenner, the universal father of immunology, whose keen observation made it possible to find inoculation against the Variola virus (1796), which was responsible for smallpox, one of the most serious, deadly and contagious infections that for centuries caused thousands of deaths. 

What results have been published in The Lancet? Volunteers injected with the vaccine developed antibodies that provide important protection and give a stronger response after a second dose as seen in the ten participants who received two doses of the vaccine.

"Both humoral and cellular immune responses are shown to have an acceptable safety profile; the humoral response is what prevents the virus from entering, and also the cellular response with T-lymphocytes, which implies that the virus enters but the cells are able to destroy those that the virus has already infected," it is indicated.

In the United Kingdom, phase I/II began last April to test the ChAdOx1 nCoV-19 vaccine that had been in use since January; in this phase, more than 1,000 healthy adults between the ages of 18 and 55 were evaluated. Ten volunteers were selected to receive two doses of the vaccine, the second at 28 days after the first. This group developed the greatest neutralizing response to the coronavirus.

The phase III clinical trial will be putting the vaccine into 30,000 volunteers in the US, and thousands more will be chosen in Brazil and South Africa, which means reaching the final stage for approval by the British health authorities.

The Oxford vaccine is not the only vaccine in the clinical trial phase, according to Jarbas Barbosa, deputy director of the Pan American Health Organization (PAHO-WHO).

A total of six trials are the most advanced to achieve effective immunization: 1) the Oxford vaccine with an agreement with the British pharmaceutical company AstraZeneca; 2) China National Pharmaceutical Group Corp. known as Sinopharm, the Chinese state company is in phase 3 in collaboration with the Institute of Virology in Wuhan has also moved to test it outside its borders on volunteers in the United Arab Emirates; 3) the American company Moderna Therapeutics will enter phase 3 of its vaccine from Monday 27 July and will start testing it in 30. 000 people in different parts of the American Union; 4) the German company BioNTech, with an agreement with the American pharmaceutical company Pfizer, will advance to phase 3 before the end of July and will start testing on 30,000 volunteers; 5) the Chinese company CanSino Biologics in phase 2 is injecting its vaccine in soldiers of its Army and the Military Scientific Institute has participated; 6) another Chinese company, Sinovac Biotech, is also about to move to phase 3 and will test its immunization both locally and in Brazil.

Russia has said that its vaccine is equally effective, the Russian press quotes both the Ministry of Defense and the Health Ministry, stating that it has been developed in collaboration with the Army and the National Center for Epidemiology and Gamaleya Microbiology; the first to be injected are military personnel.

"The Gamaleya vaccine project is based on human adenovirus, a common cold virus, mixed with the SARS CoV-2 protein to stimulate an immune response. It has some similarities to a vaccine developed by the Chinese corporation CanSino Biologics, which is already in phase 2 trials in Canada," Defense said.

Alexei Repik, director of R-Pharm, confirmed that the Russian pharmaceutical company he heads has recently signed a collaboration agreement with the British company AstraZeneca so that they can produce the Oxford vaccine in Russia for export to countries in the Middle East and Asia.

For their part, the US Department of Health and the Ministry of Defence signed an agreement with Pfizer and BioNTech for 1,950 million dollars to purchase 100 million doses of the coronavirus vaccine.

With such a large number of vaccine projects, how many coronavirus vaccines will there be? Will each country be able to supply its own, or are there international rules about this? And what will happen to countries that are not even researching how to obtain one and only have the option of buying it abroad?

To find out the official position, Barbosa insisted that the vaccine must be proven safe and effective throughout all pre-clinical trials; then it is tested in phases 1, 2 and 3 in humans, and although the last phase is definitive, it can take months because it has to be applied to groups of 30,000 to 50,000 people and see, one by one, the reactions and contraindications generated. 

But Barbosa believes that there will be vaccines, because there are dozens of other projects in phase 1 or phase 2 that could be ready by 2021 and that will allow "many opportunities" and then there is the challenge of "distributing them" equally.

The Oxford vaccine is not there yet, but a portion of the world has already shared it out because it is the most successful project: $300 million for the US, $400 million for Italy, France, Germany and the Netherlands; another $300 million for COVAX from the Fund led by WHO and PAHO for the 77 countries that are included. This sum, initially, means 1,000 million doses and the world has 7,684 million human beings.

How will it work? Can there be more than one successful SARS-CoV-2 vaccine produced by laboratories in different countries? Will the Oxford vaccine be effective?

In Alfredo Corell's opinion, if a pharmaceutical company complies with the principles of safety, efficacy and efficiency of the product and registers it, several vaccines will coexist.

"What happens is that usually in other vaccines it has been reached in a calmer way, with more tranquility; and at this moment, in the market, there will be two or three variants that coexist because the same one is for people with risk, for example, the polio there are two types of vaccines; one with inactivated microorganisms and the other not, because some produce more immunogenicity than others; that of the influenza also there are 3 or 4 presentations in the market with different substances against those that immunize or the pneumococcus equally with several presentations", explains.

According to the Spanish immunologist the existence of several presentations in the vaccines is something habitual but "the number of vaccines that are going to be concentrated by the coronavirus" is not normal.

"This is due to this frenetic race that countries have and that initially not all will have the same and it turns out that if the Oxford, Russia, China, Germany or the United States are very effective and very powerful the same and that deflates that others are generated," stresses Corell.

In an exclusive interview, the scientist and academic member of the Spanish Society of Immunology says that in Spain research is being carried out on the vaccine using the Vaccinia virus, which may be available - at a more normal rate - by the end of 2021.

"The publication by The Lancet of the results of the Oxford vaccine is very good but the most important thing is still missing: to see if it is efficient and to test it in elderly people because the trials have been in ages from 18 to 55 years," he says.

Of the side effects reported by Oxford are headaches, chills, fever and muscle aches that can be mitigated by paracetamol, in fact paracetamol is being given one day before injecting the vaccine.

What is missing then? Corell explains: "To be tested on thousands of people and to see that it is efficient; it has to complete the safety, efficacy and efficiency scheme means that it protects against the coronavirus that if the person is exposed to the virus they do not become infected is the part that is being tested.

The scale of manufacturing is global and billions of doses will be needed and manufacturers will be doing just that so there will be several vaccines from various countries and laboratories.

The million euro question, will there be a vaccine in production by September?

-I think it is a bit difficult... there are already countries that have reserved the first doses and we still do not have the vaccine.

What has this pandemic taught you as an immunologist?

- I believe that it has shaken up many of the foundations of our social functioning, but unfortunately we have learned some lessons: international solidarity and another that there is a lot of information intoxication, society does not know where to believe or who to believe, there are so many hoaxes circulating; and neither is the mixture of politics and science good, in any case the budgets must be improved to invest more in research. 

Corell, who was named the best professor in Spain in 2018, is incredulous about the US accusations against China for manufacturing the virus in a laboratory in Wuhan. The professor doubts these versions: "Here in Spain they have tested the sequence of this virus and they have seen that it is impossible as it is generated that it would have been manufactured in a laboratory. I do not believe in this conspiracy.