Vaccination, previous infection, protection from SARS-CoV-2 gamma mutants in animal models

In early January 2021, travelers returning from Amazonas in Brazil to Tokyo in Japan were screened for COVID-19 at the airport. A few days later, the National Institute of Infectious Diseases announced that travelers were returning with a new variant of the SARS-CoV-2 virus.

Its variant, known as Gamma (P.1), caused a fatal surge in COVID-19 in Brazil this spring and is now widespread worldwide. More than 200 cases have been detected in Wisconsin. It remains unclear whether current vaccines are just as effective against gamma mutants.

In a new study using a variant virus recovered from one of the original travelers, researchers in the United States and Japan found that vaccination with the mRNA vaccine was induced. Antibody reaction It protects humans from infection by the gamma / P.1 variant.Previously infected hamster Virus strain The first circulation in early 2020 was also protected from infection by the gamma mutant 9 months later.

Researchers suggest that the findings are based on previous SARS-CoV-2 infections and previous vaccines. stock The virus still provides protection against gamma infections.Published in Minutes of the National Academy of Sciences June 17, 2021.

“The animals were completely protected,” said Yoshihiro Kawaoka, a professor of virology at the University of Wisconsin-Madison Veterinary Medicine and the University of Tokyo. “Some people may be infected with this variant, even though they have been vaccinated or have been infected before, but they should not get seriously ill.”

But he says, “it doesn’t match what’s happening in Brazil.” There are reports of people re-infected with the gamma mutant after recovering from previous strain infections. According to Kawaoka, COVID-19 immunity may last longer in hamsters than in humans, or in cases recorded as reinfection may actually be the first infection.

Kawaoka’s research team showed that hamsters are highly susceptible to the SARS-CoV-2 virus and develop human-like illnesses such as opacity of frosted glass in the lungs, after showing that COVID-19 Syria last year. Established a hamster model. They also develop persistent antibodies that protect against reinfection.

“Animal models are great because they can test vaccines, drugs, monoclonal antibodies, and even pathogenesis (research),” says Kawaoka.

In fact, his team studied hamster gamma variants. Previous studies have suggested that P.1 binds well to cells and may resist antibodies produced by previous infections and vaccinations, but the ability of mutants to replicate in the body. Because little is known about. How well the disease or pathogenesis it causes, or the immune response, responds to the virus.

Researchers infected hamsters with the P.1 / gamma variant isolated from travelers, or one of two early virus strains isolated from human samples. One was isolated from the patient in February 2020 and the other is a non-variant globally predominant strain. Each strain replicated similarly in the hamster’s nose and lungs, causing similar diseases affecting the lungs.

Next, Kawaoka’s team asked whether antibodies in convalescent serum from 35 convalescent COVID-19 patients or those who received the Pfizer-BioNTech mRNA vaccine could neutralize each of the three virus strains. I checked.

Following spontaneous infection or vaccination, the body produces antibodies that learn to recognize the SARS-CoV-2 virus’s peplomer, which is involved in binding to cells. When people encounter the virus again, the antibody recognizes the spike protein and then repels or limits the extent of infection.

Previous studies have shown that peplomer mutations (E484K found in gamma variants) can alter the identity of peplomers enough to allow the mutants to bypass these defenses. However, antibodies in the blood of vaccinated individuals responded to all three strains, including gamma.

Antibodies in the blood of recovered COVID-19 patients were also effective in neutralizing each strain. However, of the 35 patients, one was infected with gamma, and antibodies from this individual were less responsive to non-mutant strains.

Researchers suggest that these findings suggest that there are some important differences in gamma peaplomers that can affect immunity and require further monitoring. In addition, Kawaoka’s group found that gamma, rather than other strains of SARS-CoV-2, could infect and replicate mice. This suggests that peplomers interact with cells in a different way than in previous strains.

Researchers also found that if a hamster recovered from infection with either of the early strains of SARS-CoV-2 was re-infected with either the same strain or the gamma mutant after 3 weeks and 9 months, in the lungs. We have found that it is protected from viral replication.

However, gamma recovered in the nasal cavities of both groups of reinfected animals. The amount of virus in the nasal cavity of re-infected animals was one-thousandth that of first-infected animals.

Finally, researchers investigated whether convalescent plasma from three patients infected with SARS-CoV-2 in early 2020 could prevent viral replication in the hamster’s nose and lungs. .. They found that convalescent plasma limits viral replication in the lungs of predominant non-mutant strains and gamma / P.1 infected hamsters, rather than plasma from patients who did not have COVID-19. discovered. The virus was found in their nasal passages.

According to Kawaoka, vaccination is the best way to seek protection from new mutants, including SARS-CoV-2 and the delta mutant, also known as B.1.617.2. The Centers for Disease Control and Prevention recently designated it as a variant of concern for evidence that the delta version is more easily transmitted.

Peter Halfman, an associate professor of research at UW-Madison and co-leader of the study, emphasized the importance of vaccination, adding that gamma and delta variants circulate in Madison and elsewhere in the United States. Did.

“Difference between original strain and (delta) and original strain and (delta)gamma) Are similar, “Kawaoka added,” the (delta) mutant can be widespread, but as long as you’re vaccinated, you don’t have to worry too much. “

As SARS-CoV-2 changes as it spreads, one of the viruses emerges when a new variant emerges, as it happened in a European variant that quickly surpassed the original virus first discovered in China in early 2020. The version of the part disappears.

“At least the majority of the population is not immune to SARS-CoV-2, so the current selective pressure against the virus is contagious,” Kawaoka said, with a trend towards new variants that have spread successfully. I will explain one reason. More contagious than the previous one. “But that will change. We should expect to see selective pressure immunize.”

This requires changing the vaccine over the next few years to protect against evolving viruses to circumvent the protection we devised, as long as the spread of the virus remains high, or if the immune system does not. That’s why it’s likely. Do not maintain protection long enough to prevent reinfection.

“I don’t know which one applies … it’s too early to say the length of immunity to this. Virus “Anyway, hamsters look different from humans. It’s hard to predict,” he said.

UW-Madison’s assistant professor Peter Halfman and Masaki Imai of the Faculty of Virus Sciences, University of Tokyo jointly led the research.