Who Has the Most Robust Antibodies to Fight Omicron?

A female healthcare professional filling a needle with the fluid from a vial of a vaccine.
Current COVID-19 vaccines seem to offer some protection against Omicron, according to early data. David Paul Morris/Bloomberg/Getty Images
  • Much remains unknown about the new coronavirus variant Omicron, and one of the biggest questions is whether vaccines will be effective against Omicron.
  • Data and real-world evidence so far shows that vaccine-induced immunity is more robust than infection-acquired natural immunity in all coronavirus variants so far.
  • However, preliminary research suggests hybrid immunity in people who previously had COVID-19 and were later vaccinated may have a higher concentration of antibodies against Omicron.
  • Pfizer has also released data confirming that a booster dose produces a similar and better antibody response than two doses alone.

The Omicron variant has been found in 57 countries and 19 states across the United States, and it continues to spread.

Many countries, including the United States, have ramped up their COVID-19 vaccine and booster rollout to better equip their populations against this new variant.

In fact, the United States recorded its highest rate for booster doses last week, administering 1 million shots per day, White House COVID-19 response coordinator Jeff Zients said Tuesday.

Amidst it all, preliminary reports have started to surface about how effective vaccines will likely be against it. So far, the data indicates that a booster dose is needed to effectively neutralize the Omicron variant.

The Pfizer vaccine vs. Omicron

Two studies were released this week on the Pfizer-BioNTech vaccine’s efficacy against Omicron.

While both of them show a reduced antibody response against Omicron, the overarching theme is that a third (booster) dose or vaccination after infection is needed for the widest range and most robust antibodies.

One study was a series of lab experiments that analyzed the immune responses of 12 people who received the Pfizer-BioNTech vaccine by experts in South Africa.

The small study, which has not yet been peer-reviewed, looked at people vaccinated with a two-dose regimen of the Pfizer vaccine, to see if the Omicron variant was better able to evade antibodies compared with the original coronavirus strain.

They found people had a 41-fold reduction in neutralizing antibodies against Omicron with the standard two-dose regimen of the Pfizer vaccine, compared with the original strain.

The study also saw that samples from people who previously had COVID-19 and were later vaccinated maintained “relatively high neutralization with Omicron” and likely had better protection than those who received two doses alone.

However, the researchers said having a booster dose was likely to produce a similar response.

Booster shot protects against Omicron

The second study was carried out by Pfizer to see if three doses would provide the adequate protection needed against Omicron.

Scientists found that three doses of the vaccine not only neutralized the Omicron variant, but also increased the neutralizing antibody titers (amounts) by 25-fold compared to only two doses.

The data also suggested that a booster dose of the Pfizer vaccine produced titers comparable with the level observed with two doses against the original virus.

Immunity is more than just antibodies

Before panicking about the drop in antibodies against Omicron, it’s important to understand how immunity works.

Human bodies have three types of immune cells, which are antibodies, memory B, and T cells.

Antibodies are the first layer of defense, and T and B cells (white blood cells) are the next layer. After successfully battling bacteria or viruses, some of these cells turn into memory cells to quickly recognize and attack them in a possible future encounter.

The body needs to produce neutralizing antibodies to recover from and protect itself against viral disease. If it can produce enough of them and fast, the body can stop the infection in its tracks.

If it doesn’t, T and B cells come in. In this fight, a subset of killer T cells, which can be induced by vaccines, play a crucial role in quelling the infection.

Fewer antibodies may mean breakthrough infections

Dr. Donald Alcendor, PhD, an associate professor of microbiology and immunology at Meharry Medical College, said current clinical findings show that individuals who have been vaccinated and boosted can have breakthrough infections with both the Delta and Omicron variant.

“There is evidence for increased transmissibility and immune evasion with the possibility of more severe disease for the [previous] variants as well as the Omicron variant because of shared mutations that have been linked to these attributes,” he said.

He explained that breakthrough infections happen when neutralizing antibodies fall to a critically low level, which is not yet known.

Several studies have shown that antibody levels start falling around the 3 to 6 month mark after vaccination. This has been one reason why booster doses have been increasingly encouraged since Omicron emerged.

Alcendor said breakthrough infections also occur when the antibodies produced by the body are insufficient to neutralize the virus.

“You need a sufficient level of neutralizing antibodies against the SARS-CoV-2 surface spike protein so that it will prevent binding to the ACE-2 protein on human lung epithelial cells to initiate an infection,” he said. 

Such cases have been seen in people who have recovered from COVID-19 but failed to produce enough or robust antibodies against the coronavirus.

Vaccines or infection?

When it comes to antibody production, vaccines seem to fare better.

Antibodies from COVID-19 infection are inconsistent

Several studies have shown that the immune response to COVID-19 infection varies greatly between individuals.

A study found that about a third of people who had COVID-19 do not develop antibodies.

A Chinese study also found that, out of 175 COVID-19 patients, 30 percent developed neutralizing antibody titers of less than 500, while 10 patients produced antibodies were under the detectable limit.

The results showed that the number of antibodies produced after a mild COVID-19 infection was highly variable, and some people may not retain any at all.

Vaccines produce more robust antibodies

COVID-19 vaccines have worked against previous variants, even Delta, which was more infectious than its predecessors.

Alcendor said, for higher levels of protection, high neutralizing antibody titers were essential.

“It has been demonstrated that neutralizing antibody titers are higher with the current vaccines than with infection,” he said.

Alcendor singled out mRNA vaccines (Pfizer-BioNTech and Moderna) for being “very efficient at provoking a powerful immune response in most people” and being “more robust than what is observed after a natural infection.”

Dr. Robert Glatter, an emergency physician at Lenox Hill Hospital, explained why vaccine-induced immunity remained superior to immunity from infection.

“The main reason is that vaccines target the spike protein, the specific area the virus attaches to the ACE-2 receptor on our cells, leading to infection and subsequent replication,” he said. “While natural infection provides immunity against important regions of the virus, vaccination specifically targets the spike protein, ensuring more specific, and therefore more robust immunity,”

Hybrid immunity may be better than just two doses

Glatter said that, although vaccine-induced immunity has an edge over infection-acquired immunity, there was one scenario where scientists saw a stronger immune response in people who had COVID-19.

“Having a prior infection and then receiving an mRNA vaccine actually leads to a more robust immune response, resulting in higher neutralizing antibody titers, compared to natural immunity alone,” he said. 

A previous study found that hybrid immunity provided protection against a wide range of variants of the virus.

The third COVID-19 jab is thought to potentially provide similar protection.

For more antibodies, a booster seems key

Glatter said it’s still not yet entirely clear how vaccine- or infection-induced immunity will measure up against the Omicron variant in real-world circumstances.

“[But] what we do know is that vaccinated and boosted individuals will be in a much better position — with a significantly higher level of neutralizing antibodies — compared to those who remain unvaccinated,” he said.

Alcendor agreed and said vaccinated people are better protected from all variants.

“You should vaccinate all children that are eligible for the vaccine, including those 5 to 11 years old. All individuals that are eligible for boosters should be boosted. Family members with underlying health conditions should be prioritized for vaccinations and boosters,” he added.

Regardless of vaccination status, Alcendor stressed that everyone should adhere to CDC mitigation guidelines of masking, social distancing in crowded spaces, and handwashing. 

“It’s vital to wear a mask indoors, especially when there will be there are large numbers of people confined to a relatively small closed space for many hours. This increases the risk of exposure significantly,” Glatter said, reminding that the virus is airborne. 

Glatter said the best way for people to protect themselves and their families is to get vaccinated and boosted.

This will confer the greatest chance at having longer-term or durable immunity, he added.

Antibody outcomes from infection alone remain unreliable, and hybrid immunity (prior COVID-19 infection followed by vaccination) seems to offer better protection against Omicron than only two doses.

A two-dose regimen and a booster dose produce significantly more antibodies and also offer good protection against Omicron.

“Adequate titers of neutralizing antibodies are required for durable or lasting immunity against not only Delta, the current dominant circulating strain, but Omicron, along with all future variants,” Glatter said.

However, he underscored that memory B cells and T cells were also a critical aspect of an intricate secondary response to infection, which are induced by vaccines.

The bottom line

Experts say that it’s likely COVID-19 vaccines will still provide some protection against the Omicron variant, even if it’s diminished.

Those who are fully vaccinated will still have some protection, as the body has seen parts of the spike protein before and produced immune cells to fight it off.

Evidence so far indicates that the current vaccines will continue to be effective against Omicron in preventing severe disease and death.

“[They have] held up against four variants of interest (VOC) including Alpha, Beta, Gamma, and Delta. The current vaccines will largely protect a completely vaccinated person from severe disease, hospitalizations, and death, which makes a good reliable vaccine,” Alcendor said.

However, more research is needed to determine how well vaccines will be in preventing symptomatic or asymptomatic COVID-19.

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