Why COVID vaccines fail to provide lasting immunity?
When the first vaccine against COVID was invented, we hoped to see the beginning of the end. However, the infection of the fully vaccinated by Delta variant shook our confidence. The more vicious Omicron-driven wave makes no distinction between the unvaccinated, the vaccinated and people with prior history of infection, smothering everyone in its wake and steering us towards dismay and despondency. So, did our belief in the COVID vaccine lead us down the garden path?
Half-life of antibody
Measles shots are good for life; the chickenpox vaccine is effective after 20 years, but why COVID-19 vaccines have failed to last long? Why does the protection against SARS-CoV-2 virus wane after a few months?
An ideal vaccine must fend against hospitalisation and deaths and prevent infection and transmission. However, not all vaccines are capable of doing that. A vaccine’s ability to avoid infection depends on how strong the immune response it elicits, the speed at which antibodies decay, the pathogen’s incubation period and how fast immune escape mutants emerge.
The magnitude of immune response the vaccine induces significantly impacts its effectiveness. Currently, all the COVID vaccines in use show robust immune responses in clinical trials. But that is not all; the antibodies once formed decay. How fast pathogen-specific antibodies decay play a hand in determining the effectiveness of vaccines.
Antibody half-life varies wildly from one pathogen to another. Researchers led by Ian J Amanna at the University of Oregon conducted a study in 2007 to estimate the antibody decay for some of the common infections. This study followed 45 subjects for more than 26 years, measuring antibodies specific to eight pathogens: measles, mumps, rubella, Epstein-Barr virus, varicella-zoster virus (chickenpox), diphtheria, tetanus and vaccinia. The half-life, i.e. the time required for the antibody levels to drop by 50%, for measles and mumps was more than 200 years, 99 years for vaccinia, 85 for rubella, 50 for the varicella-zoster virus, 11 for tetanus and 19 diphtheria. Almost no decay was detected for the Epstein-Barr virus. This is why we take a booster tetanus shot every 10 years, but the measles shot only once to protect us for lifetime.
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Alas, the SARS-CoV-2 neutralising antibodies had an average half-life of just 20.4 days. Nonetheless, it levelled out at around 90 days and did not decrease subsequently below the diagnostic cut-off values. In simple terms, most people retained seropositive antibodies for a significant period following viral infection or vaccination. Thus the COVID vaccines cannot swiftly counter the invading coronavirus but can give a good fight thereafter. The lingering antibodies, although scarce, can prevent critical illness. Hence we see a large number of mild infections even among the vaccinated. Still, minimal hospitalisation compared to the unvaccinated.
The B and T factors
Antibodies alone do not offer the whole picture. Although not well known like the antibodies, B cells and T cells play a consequential role in making the vaccine-induced immunity last longer. Vaccines train B cells and T cells, two types of immune cells key to fighting against pathogens. B cells trained by the vaccines, that is, the ‘memory’ B cells, respond when infection occurs. They rapidly deploy new antibodies to arrest the virus from infecting the host cells. The T cells develop ‘killer T cells’ that sniff out the infected cells and destroy them. The infection subsides with the invading pathogen under attract, outside the cells by B cell-induced antibodies and inside the cells by T cells.
The incubation period and the time taken for the immune system to develop protective levels of neutralising antibodies for that specific pathogen determine if the vaccines would prevent infection. The incubation period for Hepatitis B (HBV) is 45 to 160 days, while Haemophilus influenzae-type B (Hib) is less than 10 days. For COVID-19, it ranges from 1-14 days, most commonly being around 5 days.
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A long incubation period usually means more time for antibodies to ooze and build up to a protective level before the pathogen replicates significantly. When the incubation period is long, usually vaccines can ensure complete protection from infection. However, a short incubation period implies less time for the memory cells to respond with adequate levels of neutralising antibodies. Thus, often, vaccines cannot stop the infection per se but safegarud from serious illness, requiring hospitalisation.
Mutants emerge and evade
Complicating things further, often pathogens mutate and escape from immunity acquired from prior infection or vaccine. Soon after SARS-CoV-2 was detected in China, way back in January 2020, researchers began sequencing viral samples, posted the genetic codes online and were on the lookout for the emergence of variants that could evade immunity.
A million copies of the viral RNA are made inside the host infected cells. One or two of the genetic alphabets are misspelt during this copying process as the enzymes that copy RNA are prone to errors. However, a virus such as SARS-CoV-2 has a ‘proofreading’ enzyme which eliminates viral RNA copies with errors. Hence most of the mutated copies do not see the light of the day, but a few leak out of the host to infect others, creating new variants in circulation. From the genome sequencing, the researchers found that about two mutations per month occur in SARS-CoV-2, which is nearly half that of influenza and one-quarter that of HIV.
Since the commencement of the pandemic, thousands of variants have emerged, and not all of them are of interest and only a few of them fall in the category ‘variant of concern’. Most of the genome changes are silent; it hardly matters. Some of the genome changes may alter the amino acids they code and change the character of the resultant protein they go on to make. A few such changes may occur in vital spots enabling the virus to grab onto cells more tightly. Some changes can make it replicate more inside the infected cells. These changes make the variant more transmissible. Some specific mutations may empower the variant to dodge from the neutralisation by antibodies generated during previous infection or vaccination and escape.
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Not every mutant would spread. Many of the mutations disappear as quickly as they have appeared when the infected individuals isolate themselves and not transmit to others. However, few randomly get a foothold in the population and circulate far and wide, like Delta and now Omicron. Such variants of concern are now identified by a Greek letter, alpha, beta, etc.
Vaccines are not powerless in the face of mutants. In addition to the neutralising antibodies, binding antibodies contribute to viral control. A study led by Rafael Medina at the Pontifical Catholic University of Chile in Santiago shows that people immunised with vaccines maintain non-neutralising antibodies that bind Omicron and assist immune cells in gobbling up infected cells.
Vaccines protect from the post-COVID-19 syndrome
It is dawning on the medical researchers that recovery from the infection is not the end of the story. Long coronavirus disease 2019 (Long COVID19), also known as the post-COVID-19 syndrome, is an emerging and complex health problem. In addition to reducing the risk of acute illness, vaccination-induced immunity also has a protective effect against long COVID. Paul Kuodi, Azrieli, Bar-Ilan University, Safed, Israel and his colleagues studied the post COVID symptoms such as fatigue, headache, weakness and persistent muscle pain in fully vaccinated unvaccinated patients from March 2020 and November 2021. The study unequivocally showed that fully vaccinated individuals were less likely than unvaccinated individuals to report any of these symptoms.
Best protection (kavach)
Despite vaccines not being able to stop infection, it is still the only answer we have, along with masking, avoiding crowded and closed space, in our fight against the horrifying pandemic. What is a helmet to a biker is a vaccine to COVID. Wearing a helmet does not avert accidents. In a mishap, the helmet offers protection to the head, yet we may be injured in the accident. On rare occasions, the road accident may be fatal despite the helmet. Likewise, the COVID vaccines may not offer complete protection against infection but safeguard many from severe illness and secure nearly all from death. A vaccine is not a magic wand, but studies show that we are infinitely better off with it against the pandemic than without it.
(The writer is a scientist with Vigyan Prasar, Dept of Science and Technology, New Delhi)
