First-line immune defenses against COVID-19 are short-lived and may explain reinfection
A new study finds that antibodies produced in the nose decline nine months after COVID-19 infection, while antibodies found in the blood last at least a year.
Antibodies in nasal fluid (known as immunoglobulin A or IgA) provide a first-line defense against COVID-19 by blocking the SARS-CoV-2 virus when it first enters the respiratory tract. These antibodies are very effective at preventing the virus from entering cells and causing an infection.
However, the researchers found that nasal antibodies were only present in those recently infected and were particularly short-lived against the Omicron variant, compared to previous variants.
These new findings, published in eBioMedicine , may explain why people who have recovered from COVID are at risk of reinfection, and especially with Omicron and its subvariants.
The study also found that vaccination is very effective in creating and boosting antibodies in the blood, which prevent serious diseases, but had very little effect on nasal IgA levels.
First author of the study, Dr Felicity Liew, from the National Heart and Lung Institute at Imperial College London, said: “Before our study, it was unclear how long these important nasal antibodies lasted. Our study found durable immune responses after infection and vaccination, but these key nasal antibodies were shorter-lived than those in the blood. While blood antibodies help protect against disease, nasal antibodies can prevent infection altogether. “This could be an important factor behind repeated infections with the SARS-CoV-2 virus and its new variants.”
The researchers point out that studies that directly study these nasal antibodies and reinfections are needed to confirm their results.
The research was led by teams from Imperial College London and the University of Liverpool. It studied nearly 450 people who had been hospitalized with COVID-19 between February 2020 and March 2021, before the emergence of the Omicron variant and before the vaccine was launched.
The study also found that while current vaccines are effective at increasing antibodies in the blood, which can prevent serious illness and death, they do not significantly increase nasal IgA antibodies .
Researchers call for the next generation of vaccines to include nasal sprays or inhaled vaccines that target these antibodies more effectively. They say vaccines capable of boosting these antibodies could potentially reduce infections more effectively and prevent transmission.
Study co-lead author Professor Peter Openshaw, from the National Heart and Lung Institute at Imperial College London, said: “Our results highlight the need for nasal spray vaccines that can stimulate these local antibodies in the nose and lungs. . Such vaccines could prevent people from becoming infected with the SARS-CoV-2 virus and reduce transmission of the virus between people. “This could help us better control the pandemic and prevent new variants from emerging.”
He continues: “Our current vaccines are designed to reduce serious illness and death and are dramatically effective in this goal. It is now essential to also develop nasal spray vaccines that can provide better protection against infection. “It’s great that current vaccines mean fewer people get seriously ill, but it would be even better if we could prevent them from getting infected and transmitting the virus.”
The study analyzed participants’ antibodies to understand how long the nasal antibodies lasted, compared to antibodies found in the blood. They also studied the effect of subsequent COVID-19 vaccines on antibodies in the nose and blood.
Samples were taken when people were hospitalized and six months and a year later. Since most people were vaccinated during the study, many samples were also taken before and after vaccination.
They measured how well the antibodies neutralized the original SARS-CoV-2 virus and the Delta and Omicron variants to see how long the antibodies were effective after infection or vaccination.
The study included 446 people admitted to hospital in the initial phase of the pandemic, including 141 who provided samples at the beginning of the study and six and 12 months later. For participants who only had one sample taken during the 12-month study period, the researchers used models to estimate how average antibody responses changed over time.
Of those who confirmed whether they had been vaccinated (323 people), 95% (307 people) received their first vaccine during the study follow-up period. This led to increases in all nasal and blood antibodies, but the change in nasal first-line defense antibodies (IgA) was small and temporary. The researchers found that the sex, severity of illness, and age of the participants did not affect the duration of their nasal immunity, but they cautioned that their study was only in people with severe illness that required hospitalization.
They also found that participants’ blood antibodies continued to bind to the original SARS-CoV-2 virus and the Delta and Omicron variants a year after infection, but found that booster vaccines are needed to maintain this immunity.
Study co-senior author Dr Lance Turtle, senior clinical lecturer at the University of Liverpool and consultant in infectious diseases at Liverpool University Hospitals, said: “Our study suggests that this first-line defense immunity is separate of other immune responses. and although it increases with vaccination and infection, it only lasts about nine months. However, booster vaccines can increase it slightly and otherwise have a significant impact on other areas of immunity, protecting against serious illness and death very effectively, so they are still very important.”
The researchers note that their study did not screen participants for reinfection, but that this was unlikely to have occurred as the study was carried out during periods of national restrictions and lockdowns when the incidence of COVID-19 was low and people didn’t mix. In a preliminary analysis, they found only two cases of reinfection in their study, suggesting that the general trends observed are accurate.
The study was supported by the ISARIC4C, UKCIC and PHOSP-COVID consortia. It was jointly funded by the UK National Institute for Health and Care Research, Research and Innovation and the Medical Research Council.
