What Is Effective Immunity?

Can less than 100% immunity end the COVID-19 pandemic?

With the U.S. Food and Drug Administration's emergency use authorization of two COVID-19 vaccines—first Pfizer-BioNTech's tozinameran vaccine on December 11, 2020, followed by Moderna's mRNA-1273 vaccine on December 18, 202. Health officials are edging ever closer to achieving herd immunity in the United States, and hopefully towards an end to the global pandemic as we know it.

These hopes are bolstered by the fact that these vaccines are each said to afford an efficacy of over 90%, rendering what public health officials describe as "effective or practical immunity." Effective immunity is the development of antibodies to prevent infection. Effective immunity can be achieved through either infection or vaccination, and it is possible that asymptomatic infection may still occur.

Despite the positive findings, the results did not assess whether or not these vaccines provide significant sterilizing immunity. (If the immune response completely blocks infection, including asymptomatic infection, it can be referred to as sterilizing immunity.) Questions remain about how many people would need to be vaccinated in order to achieve herd immunity in the United States, and around the world.

Masked woman getting COVID-19 vaccine
 Halfpoint Images / Getty Images

Types of Immunity

Immunity, in its simplest terms, is the body's ability to resist infections. This is mediated not only by white blood cells that are central to the innate immune response—the body's in-born defense—but also antibodies that make up the adaptive (aka acquired) immune response. The innate and adaptive immune responses are each made up of complicated networks of cells that work with each other to provide immune defenses. 

The innate immune system recognizes many pathogens, but does not learn to adapt to new ones over a lifetime. On the other hand, the adaptive immune system, which is largely composed of B-cells and certain types of T-cells, learns from and responds to new challenges, and retains a memory of those challenges in later life.

Adaptive immunity can develop in one of two ways:

  • When you are infected by an infectious agent like COVID-19, during which the immune system will respond in a way that is tailor-made to that attacker and usually that attacker alone. This can include antibodies (made by B-cells) or by T-cell mediated immune responses.
  • When you are vaccinated, during which compounds are introduced into the body to stimulate a specific immune response to the disease specific to that vaccine. That immune response can last for months, years, or a lifetime long, depending on the vaccine type and a person's response to it.

With vaccines, the level of immune protection can vary as can the goals of vaccination. Some vaccines offer sterilizing immunity, in which a disease-causing pathogen is completely unable to replicate. Vaccines developed for the human papillomavirus (HPV) are one such example where viral replication is completely blocked in most vaccinated humans. 

In other instances, a vaccine can offer effective (or practical) immunity, in which the vaccine can greatly reduce the risk of infection but may not prevent asymptomatic infection. So, while the risk of illness is greatly reduced, a person can still be a carrier and able to spread the virus.

The seasonal flu vaccine, which is 40% to 50% effective in preventing infection, is an example where people who get the vaccine get the flu less often, get fewer symptoms and are less likely to transmit it to others. The current COVID-19 vaccines may fall into the same category, albeit at a far higher level of effectiveness.

As effective as the Pfizer-BioNTech and Moderna vaccines are in preventing illness, we don't know yet if they will entirely erase the risk of infection or further transmission of the virus.

How Effective Immunity Develops

Effective immunity to infections like COVID-19 requires the synthesis of specific antibodies that recognize and bind to a specific protein on the pathogen, called an antigen.

Some of these antibodies are neutralizing, meaning that they bind to a pathogen in order to prevent it from attacking and killing a host cell. Without the means to infect and replicate, a virus like COVID-19 will quickly die.

Other antibodies are non-neutralizing, meaning that they are unable to prevent infection but rather "tag" the invader for neutralization by other defensive cells.

Beyond Antibodies

There are also B cell lymphocytes (B cells), produced by the bone marrow, that become activated in the presence of an antigen, often with the help of T cells. These are the cells that actually produce antibodies.

Some of the B cells are effector cells, meaning that they are short-lived and designed to defend the body. Others are memory cells, which are long-living and serve as sentinels should the pathogen return.

If the invader does return, memory B cells can start churning out new antibodies to prevent infection or reinfection. This means that, even if the neutralizing antibodies from the COVID vaccines begin to wane, the immune system would still have "memory" of the virus and may still be able to launch a rapid immune assault.

Concerns and Challenges

The fact that the Pfizer-BioNTech and Moderna vaccines are less than 100% effective does not mean that they are less than able to bring the current pandemic under control. They can, but there are challenges.

Asymptomatic Infections

Chief among the concerns is the aforementioned risk of asymptomatic infection. Currently, without the vaccine, 1 in 5 people are believed to experience COVID-19 with no evidence of illness. With vaccination, asymptomatic disease can still occur and, with it, the risk of "silent" transmission of the virus to others. We still don’t know how well the new vaccines will prevent this from happening.

There remains some debate on how infectious asymptomatic people truly are, although the current body of evidence suggests that the risk is significantly reduced compared with symptomatic people.

According to December 2020 study from Bond University, which analyzed 13 studies from six countries, people with asymptomatic infection are 42% less likely to transmit the virus than those with symptoms.

As such, even if an infection were to occur in a vaccinated individual, it would likely be mild to asymptomatic and far less transmissable. With the rapid and effective rollout of community-wide vaccinations, the rate of infections should not only drop but also the overall virulence (severity) of COVID-19 infections.

Vaccine Durability

The one factor that scientists do not yet know is how durable the protection from the vaccines will be. Although the protection is believed to be long-lasting, in part because the virus mutates slowly, it will be some time before real-world data can support this.

While the evidence suggests that the antibody response from these RNA vaccines is strong, it will take time before scientists are able to determine how durable the response is and what quantity of memory B cells are generated after vaccination. The latter remains a concern given that antibody levels will invariably wane over time after vaccination.

Until these questions are answered, it is anyone's guess if the protection from these first-generation vaccines will be as long-lasting as many hope or require booster shots.

Moving Ahead

To better ensure herd immunity, the uptake of vaccinations among Americans not only needs to be high but fast. A slow or delayed rollout might make it more likely that an odd genetic variant resistant to the vaccine-induced antibodies could "escape" and spread, some of which may be more infectious or virulent than others.

There is concern that one such variant has already developed in Great Britain, in which changes in the virus's genome (called an H69/V70 deletion) has suggested a potential—albeit small—risk for treatment resistance. However, this variant is not suspected to have developed because of vaccine immunity,  because the variant preceded the vaccine.

By vaccinating as many Americans as quickly as possible, community infectivity can be reduced as well as the risk of viral escape mutants. The less a vaccine prevents asymptomatic infection and transmission, the more important it is to ensure the rapid distribution and uptake of the vaccine. 

This could be a challenge given ongoing troublesome public doubts about the COVID-19 vaccines, and vaccinations in general. In September 2020, prior to the news about the Pfizer-BioNTech breakthrough, only 57.6% of responders to a University of Massachusetts survey said that they were "definitely" getting the vaccine when available. However, it is encouraging that these numbers have improved since vaccine approval and rollout.

A December 2020 study in the journal Vaccine suggested similar levels of public resistance but went on to report that only 19% had a "great deal" of confidence in the safety and effectiveness of any COVID-19 vaccine.

Although these figures are likely to improve as the vaccines gain acceptance, ongoing engagement with the public is needed, particularly with regards to dispelling misinformation and restoring trust in government agencies, particularly in communities of color which have higher rates of COVID-19 infection and death, and high rates of vaccine hesitancy.

Even as concerns about the virus hopefully start to wane as more and more people get vaccinated, current public health measures including social distancing and face masks will likely need to be sustained.

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11 Sources
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