Thursday, 4 November 2021

What are ‘escape variants,’ and how are vaccine producers preparing for them?

 

  • COVID-19 vaccine companies are developing new inoculations in preparation for variants that may arise.
  • Vaccine manufacturers hope to streamline processes for faster production and approval.
  • Experts say that the current vaccines offer significant protection against the Delta variant.

Leading COVID-19 vaccine companies are working relentlessly to prepare for the possible emergence of more virulent SARS-CoV-2 variants.

A recent NatureTrusted Source news articleTrusted Source reports that AstraZeneca, Moderna, and Pfizer are updating their vaccines and running human trials to stay ahead of potential escape variants.

Escape variants are variants with the ability to evade the immunity that people acquire through vaccines and previous infections. Scientists have not identified any escape variants yet.

The manufacturers are also coordinating with regulators and streamlining internal workflows for faster deployment of vaccines if necessary.

In an August 2021 podcast that the Infectious Diseases Society of America hosted, Walter Orenstein, M.D., discussed how vaccines work. He is a professor and associate director of the Emory Vaccine Center in Atlanta.

Dr. Orenstein explained:

“The immune system functions like an army or police force. Its job is to prevent the invader, for example, a virus, from invading in the first place by creating a wall. For humans, this is antibodies, which are proteins which bind the invader […]. In addition, it has mechanisms which destroy the invader after initially invading some cells in the body but before disease can occur. This is known as cell mediated immunity.”

Dr. Orenstein said that vaccines help the immune system practice fighting pathogens. Immunizations, such as mRNA vaccinesTrusted Source, “help train the immune system to be prepared to repel an invader like a virus.”

The Nature article says that mRNA vaccine producers Moderna and Pfizer might be able to produce a prototype shot against an escape variant within days. AstraZeneca’s viral vector vaccines may take slightly longer.

Moderna, Pfizer, and AstraZeneca are taking slightly different approaches to their preparation.

Moderna

Moderna is recruiting 300–500 participantsTrusted Source to test new RNA vaccines against the Beta and Delta variants, plus a combination of Beta and the original SARS-CoV-2 variant. They will also evaluate a Beta-Delta multivalent vaccineTrusted Source that includes old and new forms of the spike protein.

According to Jacqueline Miller, Moderna’s senior vice president and head of infectious disease research, the company will turn in test cases to the Food and Drug Administration (FDA) and set up a process by which this submission can happen more quickly.

Moderna is focusing on the Beta variant because its mutations make it less sensitive to neutralization by the antibodies that the body creates following vaccination.

Pfizer

Philip Dormitzer, Pfizer’s vice president and chief scientific officer of viral vaccines and mRNA vaccinesTrusted Source, says that his company wants “to practice all aspects of executing a strain change.”

Pfizer and its partner BioNTech are testing a Beta-specific mRNA vaccine with up to 930 subjects. The companies began a clinical trial with the Delta and Alpha variants in August.

Pfizer does not see a need for a new vaccine and currently has no plans to distribute its Beta or Delta vaccines.

AstraZeneca

AstraZeneca launched a large study of a Beta-specific viral vector vaccine in June 2021. The study involves more than 2,800 individuals, many of whom have already been immunized.

The company’s executive vice-president of biopharmaceuticals research and development, Mene Pangalos, says, “We’re definitely practicing with this one, but we are also developing it, and if it’s successful, we will have it ready to use.”

The Nature article mentions several challenges of assessing the true effectiveness of variant vaccines.

Firstly, it can be difficult to find unvaccinated volunteers in some regions. Finding unvaccinated individuals willing to submit to an experimental trial may be even harder.

Recruiting placebo groups could present an ethical dilemma, as well.

Margaret Liu, M.D., chairman of the board of the International Society for Vaccines, told Medical News Today that “One of the challenges for understanding the exact impact of a variant is that the mutations can affect proteins other than spike, so there can be effects on viability and replication, etc., not just effects on how well spike binds to the ACE2 receptor or how well antibodies neutralize.”

Immunogenicity studies, which assess the immune responses that variant vaccines generate, may present a viable alternative. AstraZeneca and Moderna are pursuing this option.

The first COVID-19 vaccines are based on the SARS-CoV-2 variant identified in Wuhan, China. Virologists believe that these are sufficient for combating new variants for now.

Medical News Today asked Dr. Liu whether she expects the emerging Delta subvariant AY.4.2 to respond favorably to current vaccines.

Dr. Liu responded:

“[T]he current vaccines will likely continue to generate responses that will be useful against the AY.4.2 variant — including both antibodies and T cells. And protection from severe disease and death is still the top priority, so that is a different level of ‘favorable responses’ than protection from mild disease.”

“It still isn’t clear if or how much difference there will be compared with regular Delta in terms of infectiousness or ability to evade immune responses. The change in infectivity of Delta compared with Alpha and Alpha compared with the original [variant] was very clearly significant.”

Dr. Liu emphasized that regardless of whether the AY.4.2 subvariant exacerbates the pandemic, people should still get the vaccine and follow safety protocols. She also expressed her belief that some individuals might benefit from boosters.

It is not clear how public health authorities will determine that there is an escape variant and, therefore, that a novel vaccine is required.

Although the World Health Organization (WHO)Trusted Source has a controlled process for modifying an influenza vaccine in response to emerging variants, there is no such setup for COVID-19.

Vaccine manufacturers hope that changing a COVID-19 vaccine will become a more seamless procedure, as with flu shots. Manufacturers can also produce RNA vaccines more quickly than traditional shots.

Dr. Liu stressed that the more prevalent a virus is, the greater the possibility of variants forming and spreading. She continued:

“The more variants there are, the probability increases that one that is more deadly and/or escapes prior immune responses — whether from vaccines or from prior infection — will occur.”

Dr. Liu referred to a July 2021 monkeypox outbreakTrusted Source as a striking example of how viruses can spread:

“The person had originally flown to the [United States] from Africa. But even the people on the Atlanta-to-Dallas flight were potentially exposed. Fortunately, because everyone had to wear masks, that provided some protection. The point is that due to global travel, you really don’t know that the person you are with wasn’t exposed to a variant, even if you think of them as in your local social group. People need to live and work, but common sense can be used.”

Source: Medical News Today

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