Even Updated Bivalent COVID-19 Boosters Struggle To Prevent Sub-Omicron Transmission – Immunologist Debates Why New Methods Are Necessary

تقترح إدارة الغذاء والدواء (FDA) جرعة سنوية ضد COVID-19 ، مما يشير إلى أن هناك حاجة إلى نهج جديد.  <a href= wildpixel/iStock via Getty Images Plus src=”https://s.yimg.com/ny/api/res/1.2/OuMbNmvTp4KdHSnZUJv_Vg–/YXBwaWQ9aGlnaGxhbmRlcjt3PTcwNTtoPTM1NQ–/https://media.zenfs.com/en/the_conversation_us_articles_815/e345rcacea3sffad-data-feeca8526888cc5″ yimg

By almost every measure, the vaccination campaign against SARS-CoV-2, the virus that causes COVID-19, has been Global success.

As of January 2023, more than 12 billion Vaccines against SARS-CoV-2 have been given in an effort to save countless lives — more than 14 million In the first year of vaccine availability alone. With 95% effectiveness In preventing severe infection and death, safety features are better than similar Historically effective vaccinesThe biomedical community had hoped that a combination of vaccination and natural immunity might end the epidemic relatively quickly.

But the emergence of new viral variants, Omicron in particular And for him set of subvariablesTurned those expectations upside down. Omicron’s latest breed, XBB.1.5. — dubbed the Kraken, after a mythical sea creature — it quickly became the alternative staple in the United States. The most infectious strain to dateIts success is almost certainly attributed to the ability to evade immunity from previous vaccinations or infections.

Efforts to get ahead of these ever-changing variables is also in part what led the FDA to do so. Reconsider its approach COVID-19 Vaccine. On January 23, 2023, the agency proposed that current guidelines for a series of shots followed by a booster be replaced with an annual COVID-19 vaccine updated each year to combat current strains. The proposal is scheduled to be reviewed by the FDA’s Scientific Advisory Committee on January 26.

Limitations of current mRNA vaccination strategies

Unfortunately, the new bivalent shots, which include ingredients from the original SARS-CoV-2 strain as well as the latest omicron variant, have did not perform as well As some scholars had hoped. Although there is no doubt that the updated Strikes are capable of this Increased antibody levels against SARS-CoV-2 and Help prevent severe illness and hospitalizationAnd several studies They have suggested that they are not necessarily better able to prevent omicron infection than their ancestors.

like Immunologist Who studies how the immune system works Selects the antibodies that are produced And Immune responses to COVID-19These new results are disappointing. But it’s not entirely unexpected.

When the COVID-19 vaccines were rolled out in early 2021, immunologists began to do so Public discussions On potential barriers to rapidly generating updated vaccines for emerging viral strains. At that time, there was no confirmed data. But the researchers knew of very long time That immune memory, the thing that provides continued protection against the virus long after vaccination, can sometimes negatively interfere with development. Updated immune responses.

The failure of these new bivalent vaccines to prevent large-scale omicron infection indicates that our current approach is simply not sufficient to disrupt the cycle of viral transmission leading to the COVID-19 pandemic. In my view, it is clear that there is a great need for innovative vaccine designs capable of producing broader immunity.

Vaccines are designed to generate an immunological memory

In simpler terms, vaccines are a way to give your immune system a peek at a pathogen. There are several different ways to do this. One way is to inject, as it were, inactivated copies of the virus Ended with polio. Another is the use of non-infectious viral components, such as the proteins used Flu vaccines.

More recently, scientists have found ways to deliver mRNA The “instructions” that tell your body How to make those non-infectious viral components. This is the approach used with Moderna and Pfizer vaccines Targeted against COVID-19.

All mRNA-based vaccines train your immune system to recognize and respond to key components of a potential invasion. An important part of this response is getting your body to produce antibodies that will hopefully prevent future infections, helping to break the cycle of person-to-person transmission.

In a successful response, the immune system will not only produce pathogen-specific antibodies, but will also remember how to make them if it encounters the same pathogen again in the future.

أثبت النهج الحالي للقاحات COVID-19 فعاليته في الوقاية من الأمراض الخطيرة والوفاة ، لكنه لم يمنع العدوى كما كان يأمل العلماء.  <a href= Images by MRSA/DigitalVision via Getty Images data-src=”https://s.yimg.com/ny/api/res/1.2/6gHHH4G9Vz4NOy1DF3vb8Q–/YXBwaWQ9aGlnaGxhbmRlcjt3PTcwNTtoPTQ3MA–/https://media.zenfs.com/en/the_conversation_us_articles_815/2ad4180e473cf300e475bf300″>
The current approach to COVID-19 vaccines has proven effective in preventing serious illness and death, but it hasn’t prevented infection as well as scientists had hoped. Marina Images/DigitalVision via Getty Images

The specter of “original sin of the antigen”

But what happens when the virus evolves and that memory becomes obsolete?

Immunologists have wondered about this Since the initial COVID-19 vaccine was introduced. Recently, he found new significance in the light FDA proposal For an updated annual COVID-19 snapshot.

While it is possible that the immune responses to vaccines updated Simply replace the old oneThis was not true of the flu. With influenza, researchers have learned that immunity is pre-existing to one strain can actively prevent The ability to respond well against the other.

Put everyday language, think of a virus as a car trying to run you over. You can produce one type of antibody against the hood, one against the bumper and one against the hubcaps that keep the wheels from turning. It produced three car-specific antibodies, but it turned out that only the hubcap antibody effectively slowed it down.

Now the vehicle is changing, like SARS-CoV-2. Reshape the joint caps or remove them completely. Your immune system still recognizes the car, but not the hubcaps. The system doesn’t know that the hubcap was the only effective target, so it ignores the hubcaps and increases its attack on the hood and bumper.

Ignoring the new hubcap response, the immune system’s memory of the original car is not only outdated, but it also interferes with the response needed to target the wheels of the new car. This is what immunologists callOriginal antigenic sinAn ineffective immune memory that impairs desirable responses to new strains of pathogens.

This type of overlap has been very difficult to identify and study in humans, although it may become easier with FDA proposal. The once-a-year approach to coronavirus vaccination opens the door to more direct studies of how the memory of each vaccine affects the next.

Multistrain vaccinations offer hope

together, great efforts They are conducted to prioritize the pursuit of a single vaccine or a “universal” vaccine. One approach has been to take advantage of emerging research showing that if multiple versions of the same pathogen are presented to your immune system, it will tend to Choose common goals.

Presented with the Model T, Ford F-150, and electric Mustang simultaneously, your immune system often chooses to ignore differences like hubcaps in favor of similarities like shape and rubber on the tires. Not only would this interfere with the function of all three vehicles, but it could theoretically interfere with most vehicles on the roads – or viral threats such as variants.

Researchers have begun to make rapid progress using this approach with the development of Multistrain complex influenza vaccines which is doing well in early clinical trials. New studies have focused on SARS-CoV-2 I hope you will do the same. Chronic pathogens incl flu And Immunity deficiency Virus They all suffer from versions of the same antibody targeting issues. This pandemic can be a crucible for innovation that leads to the next generation of infectious disease prevention.

This is an updated version of an article Originally published on March 8, 2021.

This article has been republished from Conversation, an independent, nonprofit news website dedicated to sharing ideas from academic experts. If you find it interesting, you can Subscribe to our weekly newsletters.

written by: Matthew WoodruffAnd Emory University.

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Matthew Woodruff does not work for, consult with, own stock, or receive funding from any company or organization that would benefit from this article, and has not disclosed any relevant affiliations beyond their academic appointment.

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