A top infectious disease physician explains why immunity derived from natural infection and the vaccines should be long-lasting.
There are two major arms of the immune system: B cells (which produce antibodies) and T cells (which are formed specifically to attack and kill pathogens). T cells are divided into two types, CD4 cells ("helper" T cells) and CD8 cells ("cytotoxic" T cells).
Each arm, once stimulated by infection or vaccine, should hopefully make "memory" banks. So if the body sees the pathogen in the future, these defenses should come roaring back to attack the virus and protect you from getting sick. Plenty of research in COVID-19 indicates a likely long-lasting response to the vaccine or infection. Here are seven of the most compelling reasons:
REASON 1: Memory B Cells Are Produced By Vaccines and Natural Infection
In one study, 12 volunteers who had never had Covid-19--and were fully vaccinated with two Pfizer/BioNTech shots-- underwent biopsies of their lymph nodes. This is where memory B cells are stored in places called "germinal centers". The biopsies were performed three, four, six, and seven weeks after the first mRNA vaccine shot, and were stained to reveal that germinal center memory B cells in the lymph nodes increased in concentration over time.
Natural infection also generates memory B cells. Even after antibody levels wane over time, strong memory B cells were detected in the blood of individuals six and eight months after infection in different studies. Indeed, the half-lives of the memory B cells seen in the study examining patients 8 months after COVID-19 led the authors to conclude that "B cell memory to SARS-CoV-2 was robust and is likely long-lasting." Reason #2 tells us that memory B cells can be active for a very long time indeed.
REASON #2: Memory B Cells Can Produce Neutralizing Antibodies If They See Infection Again Decades Later
Demonstrated production of memory B cells after vaccination or natural infection with COVID-19 is so important because memory B cells, once generated, can be activated to produce high levels of neutralizing antibodies against the pathogen even if encountered many years after the initial exposure. In one amazing study (published in 2008), researchers isolated memory B cells against the 1918 flu strain from the blood of 32 individuals aged 91-101 years. These people had been born on or before 1915 and had survived that pandemic.
Their memory B cells, when exposed to the 1918 flu strain in a test tube, generated high levels of neutralizing antibodies against the virus -- antibodies that then protected mice from lethal infection with this deadly strain. The ability of memory B cells to produce complex antibody responses against an infection nine decades after exposure speaks to their durability.
REASON #3: Vaccines or Natural Infection Trigger Strong Memory T Cell Immunity
All of the trials of the major COVID-19 vaccine candidates measured strong T cell immunity following vaccination, most often assessed by measuring SARS-CoV-2 specific T cells in the phase I/II safety and immunogenicity studies. There are a number of studies that demonstrate the production of strong T cell immunity to COVID-19 after natural infection as well, even when the infection was mild or asymptomatic.
The same study that showed us robust memory B cell production 8 months after natural infection also demonstrated strong and sustained memory T cell production. In fact, the half-lives of the memory T cells in this cohort were long (~125-225 days for CD8+ and ~94-153 days for CD4+ T cells), comparable to the 123-day half-life observed for memory CD8+ T cells after yellow fever immunization (a vaccine usually given once over a lifetime).
A recent study of individuals recovered from COVID-19 show that the initial T cells generated by natural infection mature and differentiate over time into memory T cells that will be "put in the bank" for sustained periods.
REASON #4: T Cell Immunity Following Vaccinations for Other Infections Is Long-Lasting
Last year, we were fortunate to be able to measure how T cell immunity is generated by COVID-19 vaccines, which was not possible in earlier eras when vaccine trials were done for other infections (such as measles, mumps, rubella, pertussis, diphtheria). Antibodies are just the "tip of the iceberg" when assessing the response to vaccination, but were the only arm of the immune response that could be measured following vaccination in the past.
Measuring pathogen-specific T cell responses takes sophisticated technology. However, T cell responses, when assessed years after vaccination for other pathogens, has been shown to be long-lasting. For example, in one study of 56 volunteers who had undergone measles vaccination when they were much younger, strong CD8 and CD4 cell responses to vaccination could be detected up to 34 years later.
REASON #5: T Cell Immunity to Related Coronaviruses That Caused Severe Disease is Long-Lasting
SARS-CoV-2 is a coronavirus that causes severe disease, unlike coronaviruses that cause the common cold. Two other coronaviruses in the recent past caused severe disease, specifically Severely Acute Respiratory Distress Syndrome (SARS) in late 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2011.
A study performed in 2020 demonstrated that the blood of 23 recovered SARS patients possess long-lasting memory T cells that were still reactive to SARS 17 years after the outbreak in 2003. Many scientists expect that T cell immunity to SARS-CoV-2 will be equally durable to that of its cousin.
REASON #6: T Cell Responses from Vaccination and Natural Infection With the Ancestral Strain of COVID-19 Are Robust Against Variants
Even though antibody responses from vaccination may be slightly lower against various COVID-19 variants of concern that have emerged in recent months, T cell immunity after vaccination has been shown to be unperturbed by mutations in the spike protein (in the variants). For instance, T cell responses after mRNA vaccines maintained strong activity against different variants (including P.1 Brazil variant, B.1.1.7 UK variant, B.1.351 South Africa variant and the CA.20.C California variant) in a recent study.
Another study showed that the vaccines generated robust T cell immunity that was unfazed by different variants, including B.1.351 and B.1.1.7. The CD4 and CD8 responses generated after natural infection are equally robust, showing activity against multiple "epitopes" (little segments) of the spike protein of the virus. For instance, CD8 cells responds to 52 epitopes and CD4 cells respond to 57 epitopes across the spike protein, so that a few mutations in the variants cannot knock out such a robust and in-breadth T cell response. Indeed, a recent paper showed that mRNA vaccines were 97.4 percent effective against severe COVID-19 disease in Qatar, even when the majority of circulating virus there was from variants of concern (B.1.351 and B.1.1.7).
REASON #7: Coronaviruses Don't Mutate Quickly Like Influenza, Which Requires Annual Booster Shots
Coronaviruses are RNA viruses, like influenza and HIV (which is actually a retrovirus), but do not mutate as quickly as either one. The reason that coronaviruses don't mutate very rapidly is that their replicating mechanism (polymerase) has a strong proofreading mechanism: If the virus mutates, it usually goes back and self-corrects. Mutations can arise with high rates of replication when transmission is very frequent -- as has been seen in recent months with the emergence of SARS-CoV-2 variants during surges. However, the COVID-19 virus will not be mutating like this when we tamp down transmission with mass vaccination.
In conclusion, I and many of my infectious disease colleagues expect the immunity from natural infection or vaccination to COVID-19 to be durable. Let's put discussion of boosters aside and work hard on global vaccine equity and distribution since the pandemic is not over until it is over for us all.
Paul Alexander spent more than 70 years confined to an iron lung after a polio infection left him paralyzed at age 6. Here, Alexander uses a mirror attached to the top of his iron lung to view his surroundings.
Paul Alexander was one of several thousand who were infected and paralyzed by polio in 1952. That year, a polio epidemic swept the United States, forcing businesses to close and polio wards in hospitals all over the country to fill up with sick children. When Paul caught polio in the summer of 1952, doctors urged his parents to let him rest and recover at home, since the hospital in his home suburb of Dallas, Texas was already overrun with polio patients.
Paul rested in bed for a few days with aching limbs and a fever. But his condition quickly got worse. Within a week, Paul could no longer speak or swallow, and his parents rushed him to the local hospital where the doctors performed an emergency procedure to help him breathe. Paul woke from the surgery three days later, and found himself unable to move and lying inside an iron lung in the polio ward, surrounded by rows of other paralyzed children.
Hospitals were commonly filled with polio patients who had been paralyzed by the virus before a vaccine became widely available in 1955. Associated Press
But against all odds, Paul lived. And with help from a physical therapist, Paul was able to thrive—sometimes for small periods outside the iron lung.
The way Paul did this was to practice glossopharyngeal breathing (or as Paul called it, “frog breathing”), where he would trap air in his mouth and force it down his throat and into his lungs by flattening his tongue. This breathing technique, taught to him by his physical therapist, would allow Paul to leave the iron lung for increasing periods of time.
With help from his iron lung (and for small periods of time without it), Paul managed to live a full, happy, and sometimes record-breaking life. At 21, Paul became the first person in Dallas, Texas to graduate high school without attending class in person, owing his success to memorization rather than taking notes. After high school, Paul received a scholarship to Southern Methodist University and pursued his dream of becoming a trial lawyer and successfully represented clients in court.
Paul Alexander, pictured here in his early 20s, mastered a type of breathing technique that allowed him to spend short amounts of time outside his iron lung. Paul Alexander
Throughout his long life, Paul was also able to fly on a plane, visit the beach, adopt a dog, fall in love, and write a memoir using a plastic stick to tap out a draft on a keyboard. In recent years, Paul joined TikTok and became a viral sensation with more than 330,000 followers. In one of his first videos, Paul advocated for vaccination and warned against another polio epidemic.
Paul was reportedly hospitalized with COVID-19 at the end of February and died on March 11th, 2024. He currently holds the Guiness World Record for longest survival inside an iron lung—71 years.
Polio thankfully no longer circulates in the United States, or in most of the world, thanks to vaccines. But Paul continues to serve as a reminder of the importance of vaccination—and the power of the human spirit.
““I’ve got some big dreams. I’m not going to accept from anybody their limitations,” he said in a 2022 interview with CNN. “My life is incredible.”
