Do we need a multivalent universal vaccine for coronavirus mutations?

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Do we need a multivalent universal vaccine for coronavirus mutations?

Do we need a multivalent universal vaccine for coronavirus mutations?. As of April 28, local time, India has added more than 300,000 new cases of new coronavirus pneumonia in a single day for the seventh consecutive day.

Soumya Swaminathan, the chief scientist of the World Health Organization (WHO), said that the actual number of infections in India may be 20-30 times higher than the official report. This means that the cumulative number of infections in India may have been close to 530 million.

At present, the first batch of anti-epidemic materials supported by the United Kingdom, the United States, and China has arrived in India. This week, another 10,000 oxygen generators supported by China will also arrive in the country.

“India is struggling. Sadly, the situation may deteriorate further in the next few weeks.” The British Broadcasting Corporation (BBC) quoted Shahid Jah, a virologist and dean of the Trividi School of Biological Sciences at Ashoka University in India. Shahid Jameel said in a speech that the mathematical model shows that if there is no effective control, by the first week of May, the number of newly diagnosed cases in India in a single day may rise to 500,000, and the number of new deaths in a single day may exceed 5,700.

“The situation in India is similar to Brazil, Iran, etc.” Kristian Andersen, an infectious disease scientist at the Scripps Institute in the United States, told the National Public Radio (NPR) that these countries had previously had extremely high infection rates. , And a serum sample survey shows that it may achieve herd immunity to some extent. But the reality is that a new wave of epidemics has appeared in the above-mentioned countries one after another, which is more menacing and even worse than before.

A large number of analyses believe that the emergence and spread of mutant strains of the new coronavirus is one of the reasons for the rapid deterioration of the epidemic situation in countries such as India. “In the Indian epidemic, the main lesson is that it resumed social activities prematurely, the government made wrong decisions and the people relaxed their vigilance. There is no clear evidence to support these mutants. These mutants are more suitable, faster to spread, and more toxic. I maintain The original view was that the new coronavirus did not mutate so quickly, and no major mutations made the existing vaccines completely invalid. The mutant strains are worthy of vigilance, but there is no need to talk about discoloration.” Professor Jin Dongyan, a well-known virology expert and the School of Biomedicine, University of Hong Kong, told “Medical Science” World”.

Do we need a multivalent universal vaccine for coronavirus mutations?
Photo caption: On April 21, 2021, a large number of people who died of COVID-19 were cremated in the open air at a crematorium in New Delhi, the capital of India. /AP

Where has the virus changed?

The Indian digital news platform “The Print” reported on April 23 that there are multiple COVID-19 mutant strains circulating in India. The highest infection rate is B.1.617. In the severely affected area of Maharashtra, the detection rate rose from 11% in January 2021 to more than 50% in March.

The mutant strain B.1.617 was first discovered on October 5, 2020 in the densely populated city of Nagpur in central India. “Many people and the media-including NPR-call it a double mutant strain.” NPR reports.

“The term’double mutation’ is not accurate.” On April 26, virologist Shahid Jamil was interviewed by the Shillong Times of India. B.1.617 contained 15 mutations, and 6 of them occurred in the virus. On the spike protein, L452R, D614G and P681R are more critical.

Information from the World Health Organization (WHO) shows that the D614G mutation in June 2020 has become the dominant strain spreading globally, and it is more infectious than the previous strain. Research on the mutations of L452R and P681R claims that it may enable the virus to enter cells more efficiently and increase infectivity.

“B.1.617 is evolving and diverging over time, which increases uncertainty.” The Financial Times quoted Sharon Peacock, director of the British Federation of New Coronavirus Disease Genomics, as saying that science The world has discovered three descendant lineages of B.1.617, namely B.1.617.1, B.1.617.2 and B.1.617.3. The difference lies in the presence or absence of E484Q mutations, which may enhance the virus’s escape immunity.

According to the latest WHO data on April 27, at least 17 countries have reported the discovery of the mutant strain B.1.617, mainly imported cases from India.

However, many Indian experts believe that B.1.617 is not the main cause of the second wave of the epidemic in India. The first institution to sequence the gene of B.1.617 was the Cell and Molecular Biology Center of the Indian Council of Science and Industry Research in Hyderabad. Center director Rakesh Mishra (Rakesh Mishra) said that B.1.617 only accounts for 10% of the new coronavirus samples sequenced in India and has not become the main epidemic strain in India. “The second wave of epidemics is more due to the public’s lax attitude towards epidemic prevention, and failure to strictly follow epidemic prevention regulations such as wearing masks and maintaining social distancing.”

“Genome sequencing is the only reliable way to track mutant strains. But the problem is that compared to the 1.4 billion population, India uploads and shares very few genome sequencing.” “The Print” quoted data from the Global Influenza Shared Database (GISAID), GISAID. More than 1200 copies of B.1.617 genome sequencing results have been received. Among them, India submitted about 800 results, which is not proportional to its huge number of infections.

“The role of mutant strains in the new round of outbreaks in India is not yet known.” Jeffrey Barrett, head of the COVID-19 Genome Project at the Wellcome Sanger Institute in the United Kingdom, told the Financial Times that a variety of things may be happening in India. The virus strains overlap.

Mutant strains affect vaccine effectiveness?

On April 27, the WHO released the latest global weekly report on the new coronavirus epidemic, which classified the new coronavirus mutant strains into two categories: “Noticeable” (VOI) and “Special Concern” (VOC). Seven mutant strains including B.1.617 are listed as VOI. At the same time, there are 3 main epidemic mutant strains belonging to VOC, namely B.1.351 which first appeared in South Africa in August 2020, B.1.1.7 which first appeared in the United Kingdom in September, and appeared in Brazil and Japan in December of the same year. P.1.

These three VOC mutant strains all have N501Y and D614G mutations on the viral spike protein. Past studies have shown that related mutations may enhance the spread and pathogenicity of the virus. Recently, journals including “Cell”, “The Lancet · Infectious Diseases”, “The Lancet · Public Health” and “New England Journal of Medicine” have successively published articles stating that the three VOC mutant strains show stronger transmission ability.

The above-mentioned journal also pointed out that both South Africa’s B.1.351 and Japan’s P.1 have E484K mutations, which may evade immunity, resulting in reduced vaccine effectiveness. Taking the mutant strain B.1.351 as an example, the AstraZeneca adenovirus vaccine has a preventive effect of only 10% against mild to moderate infections.

In addition, Professor Dayi He, a foreign academician of the Chinese Academy of Engineering, posted on the pre-printed platform bioRxiv that the seroprotective efficacy of patients vaccinated with the two new mRNA vaccines against this mutant strain is only 1/9 to 1/6, and 20 new coronavirus pneumonia patients have recovered. The seroprotective effect of the patient is only 1/33 to 1/11. Recently, Professor Dayi He delivered a keynote speech “Thinking about the mutation of the COVID-19 virus” at the “Yunfeng Future Medical Forum”. He used “tricky” to describe the E484K mutation.

“The scientific community attaches great importance to B.1.617 because the E484Q mutation that occurs is similar to the E484K mutation,” said virologist Shahid Jamil.

Florian Krammer, a vaccine researcher at the Icahn School of Medicine at Mount Sinai in the United States, disagrees. “The two mRNA COVID-19 vaccines can induce very high levels of antibodies, which can compensate for the decline in protective efficacy. In addition, neutralizing antibodies are only part of the immune response, and the vaccine can also stimulate T cells.” He said he was “optimistic” and believed that now Vaccines can still prevent B.1.351 and P.1 mutant strains.

“The rapid change in the number of infections in South Africa may also show that B.1.351 is not as terrible as imagined.” According to an analysis by the Financial Times, at the end of 2020, as many as one-third of confirmed cases in severely affected areas in South Africa were infected with the mutant strain B.1.351. . At that time, the South African medical community prepared for the worst. However, after January 2021, in the absence of mass vaccination or strict lockdown, the number of newly diagnosed people in South Africa has dropped from a historical high of nearly 22,000 to about 1,000.

Jinal Bhiman, chief medical scientist at the National Institute of Infectious Diseases in South Africa, believes that the simplest explanation is that past infections have caused herd immunity, thereby blocking the spread of the virus. “But this is full of uncertainties. Due to the limited detection capacity and the high number of asymptomatic infections, South Africa does not know the true damage caused by the mutant strain.”

“From the changes in the epidemic situation in South Africa, we can see that the COVID-19 epidemic has its own development pattern. Now’it’s not that the sky is falling down’.” Jin Dongyan said.

“Customized” version B.1.351 vaccine, or hope of anti-epidemic?

There is some experts pointing out the final result of the mutation of the new coronavirus may become a popular but poorly fatal conventional disease. The theoretical basis is that the deadly mutant virus will cause the death of the host, but affect the spread.

Yang Zhanqiu, a professor at the Institute of Virology at the Wuhan University School of Medicine, told the Global Times that, at the moment, this statement is a bit premature. On the one hand, with the mutation speed of the existing virus, this situation is unlikely to occur in the short term. On the other hand, the only way for humans to completely eliminate the new coronavirus is a vaccine. After the vaccine is injected, the human body’s ability to resist the virus changes, which will lead to a decline in the ability of the virus to spread. However, it has taken a long time to achieve full coverage of vaccines globally.

The team of Professor Eyal Leshem from the Chaim Sheba Medical Center in Israel published a review article in The Lancet that in the case of unnatural infections, nearly 100% of the population needs to be vaccinated or 80%. % Of people receive two doses of vaccine to stop the spread of the new coronavirus.

“Mutations themselves are random, but in the process of fighting humans, those mutations that enhance infectivity and have the ability to escape immunity will be highlighted and become the mainstream in the epidemic.” Professor Dayi He believes that along with With the development of the pandemic, more and more new coronavirus mutant strains appear, and antibody treatment strategies need to be updated in real time.

At present, many vaccine manufacturers have begun to study vaccines against mutant strains. On the 24th of this month, at the 2021 Frontiers of Medical Science Forum of the Chinese Academy of Engineering in Guangzhou, Zhong Nanshan, an academician of the Chinese Academy of Engineering, also said through the connection: “We are fully developing vaccines against mutant strains.”

At the end of February, Moderna of the United States announced that it had initiated the development of a new coronavirus vaccine mRNA-1273.351 against the B.1.351 mutant strain. At the same time, Sarah Gilbert, a professor at the University of Oxford in the United Kingdom, said that clinical trials of an adenovirus vaccine against the B.1.351 mutant strain will begin this summer, and the vaccine may be on the market this fall.

“B.1.351 infection can cause a wide range of responses to resist new and old mutant strains. This is a surprise.” In March, the journal Nature quoted Penny Moore, an associate professor at the National Institute of Infectious Diseases in South Africa, saying that related research showed that, The antibodies produced by those who were infected with B.1.351 and recovered can block the infection of mutant strains such as P.1 well. These mutant strains share common mutations with B.1.351.

In addition, the French company Valneva and the German CureVac company have reported that they will develop a “multivalent” COVID-19 vaccine, that is, a single injection containing multiple strains. The French company Valneva stated that the inactivated vaccine it is developing uses a complete virus, which may allow the immune system to respond to various epitopes. Epitope refers to the part of the viral protein that the immune system can recognize.

“At the beginning of the outbreak, some people proposed to develop a multivalent universal vaccine, or to protect vaccinators from the COVID-19, SARS, MERS and other coronavirus infections at the same time.” Jin Dongyan said that these mostly stay in theory, and there is no mature plan or no. actual needs.

Jin Dongyan said that there is currently no evidence that there have been mutants that completely escape the protection of the vaccine and have a major impact on the epidemic. “But we need to be alert to potential dangers. During the rapid rise of the epidemic, the large-scale use of less protective vaccines may stimulate the emergence of vaccine escape variants. Countries should monitor them. Once the vaccine escape strain is confirmed, existing technologies can be used. Quickly prepare new vaccines.”

“It is too early to develop a new vaccine to solve the mutant strain. It has not yet reached the critical line.” Paul Offit, a specialist in infectious diseases at the Children’s Hospital of Philadelphia and director of the Vaccine Education Center, pointed out that crossing the critical line means A large number of people who are naturally infected or who have been vaccinated are re-infected with the new coronavirus, and the condition is so serious that they need to be hospitalized.

He said that the new coronavirus mutates more slowly than the flu virus. In the next few months, enough people will be vaccinated. Coupled with a considerable number of people already infected, the virus transmission rate is expected to decline. As long as the spread slows, the possibility of virus mutation will also decrease.

In the eyes of Sharon Pickacock, director of the British Federation of New Coronavirus Disease Genomics, once the virus can be suppressed, or the virus mutated into a non-toxic and non-disease, humans will be able to sit back and relax. “But at present, we need to continue to fight against the COVID-19 epidemic for the next 10 years,” she told the BBC.

(source:internet, reference only)

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