Study Shows Prior Infection Offers Strong Immunity to Original COVID-19 Strain

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Study Shows Prior Infection Offers Strong Immunity to Original COVID-19 Strain

Unprecedented human challenge studies of active infection with COVID-19 suggest that prior infection or vaccination can induce effective protective immunity.

Individuals without antibodies against specific infectious agents are called “seronegative,” while those with antibodies are called “seropositive.” Due to the prolonged global spread of the SARS-CoV-2 virus and widespread vaccination against COVID-19, most people have either been infected, vaccinated, or both, resulting in the development of antibodies against the virus. This means that finding “seronegative” volunteers is becoming increasingly difficult.

To aid in vaccine development, researchers at the University of Oxford previously established a Controlled Human Infection Model (CHIM) in “seronegative” volunteers, where healthy volunteers were deliberately infected with the SARS-CoV-2 virus under very carefully controlled clinical conditions. With the proportion of “seropositive” individuals increasing, the CHIM used for vaccine development now needs to actively induce infection in immune individuals (i.e., “seropositive” individuals). CHIMs can be used to rapidly test or compare new vaccines or treatments in a controlled environment, as well as to reveal what kind of immune response can prevent reinfection in individuals who have had prior infection and/or vaccination.

On May 1, 2024, the research team published a study titled “Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study” in The Lancet Microbe.

This unprecedented human challenge study investigated the human immune response to the SARS-CoV-2 virus in individuals who already have antibodies against it, either through previous infection or vaccination. The results indicate that prior infection or vaccination can provide strong protection against the original strain of the SARS-CoV-2 virus.

Study Shows Prior Infection Offers Strong Immunity to Original COVID-19 Strain

In this study, the research team recruited 36 healthy volunteers aged 18-30 who had previously experienced SARS-CoV-2 infection (with or without vaccination) and inoculated them with increasing doses of the original strain of the SARS-CoV-2 virus in a CHIM (1×101, 1×102, 1×103, 1×104, or 1×105 TCID50 by nasal administration). After inoculation, these volunteers were isolated in negative pressure rooms for 14 days until they tested negative on a combined nasopharyngeal swab test at 12 hours. Subsequently, these volunteers were followed up for 12 months, with additional follow-ups for those who experienced reinfection. The primary aim was to determine a safe, well-tolerated dose that would induce infection in 50% of seropositive volunteers.

Recruitment for the study began on May 6, 2021, with the last volunteer joining on November 24, 2022. All volunteers completed isolation and were followed up for 12 months. The results of the study showed that even when the dose of the SARS-CoV-2 virus was increased to 1×105 TCID50, no sustained infection was induced in any of the volunteers, with PCR testing showing that 5 out of the 36 volunteers (14%) had transient infection. Volunteers with transient infection had significantly lower mucosal and systemic antibody titers specific to the SARS-CoV-2 virus at baseline, as well as significantly lower peripheral IFNγ responses to a library of SARS-CoV-2 peptides for CD8+ T cells, compared to those who were not infected. Most of the adverse events reported by volunteers during isolation were mild, with the most common being fatigue (44%) and nasal congestion (44%), and no serious adverse events occurred. Fourteen out of the 36 volunteers (39%) experienced breakthrough infections with the Omicron variant after isolation was lifted.

These findings demonstrate that prior infection/vaccination confers durable immunity against the original strain of the SARS-CoV-2 virus. By comparing the immune responses of volunteers infected in the trial with those not infected, the study found that antibody levels in the nasal mucosa may be important for preventing mild infection. Additionally, volunteers who were not infected with the original strain in the trial experienced breakthrough infections with the Omicron variant, prompting further investigation by the research team using a CHIM with novel variant strains to assess new vaccines or COVID-19 treatments.

Lead researcher Professor Helen McShane stated that this is a very important proof-of-concept study, demonstrating that controlled human infection studies can be conducted safely during a pandemic and can provide valuable information that is difficult to obtain through traditional field studies. It is hoped that this will provide confidence in using human infection studies as a tool for developing improved COVID-19 vaccines and therapies, as well as for future pandemics.

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