Study characterizes COVID-19 vaccine effectiveness at longer dose intervals

By Neha MathurFeb 18 2022Reviewed by Aimee Molineux

In a recent study published in the New England Journal of Medicine, researchers conducted a prospective cohort study in the UK to assess the level and durability of protection offered by two doses of coronavirus disease 2019 (COVID-19) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in participants with no history of a previous infection. 

The researchers evaluated vaccine effectiveness (VE) after two doses of the COVID-19 vaccine, according to the type of vaccine and dosing interval; additionally, they determined immunity against reinfection conferred together by previous infection and vaccination.

Although several studies have reported the short-term VE of the COVID-19 vaccine, studies investigating the long-term VE of vaccines for symptomatic and asymptomatic SARS-CoV-2 infection, COVID-19 severity, and secondary transmission are still sparse. The characterization of VE at longer dose intervals, accounting for the efficacy variations due to demographic factors, vaccination schedules, and history of SARS-CoV-2 infection are warranted to inform vaccination strategies.

About the study

The UK health care workers who participated in the multicenter cohort study SIREN were assigned one of the two study groups - the previously uninfected cohort having no history of SARS-CoV-2 infection and the previously infected cohort with individuals who at least once tested SARS-CoV-2-positive.

A total of 44,546 participants enrolled for SIREN from 135 sites across the UK between June 18, 2020, and April 23, 2021. Of these, only 35,768 met the inclusion criteria for this analysis. The median age of the participants was 46 years, and 84% of them were women.

During the study period, subjects underwent reverse transcriptase-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2, lateral-flow testing every two weeks, and a monthly antibody test. Every two weeks, they filled out questionnaires inquiring about their COVID-19 symptoms.

The researchers gathered the vaccination data of the study participants from a national vaccination register, although each participant provided vaccination-related data every two weeks via questionnaires as well. In a ‘short’ dosing interval, the second dose was administered any time during six weeks after the first dose, whereas in a ‘long’ dosing interval, it was after six or more weeks.

The researchers used the Elecsys anti-SARS-CoV-2 nucleocapsid (N) protein assay and anti-SARS-CoV-2 spike (S) protein assay to test serum samples of all the participants collected centrally during their baseline visits.

Findings

At the commencement of the analysis, there were 26,280 and 9,488 participants in the previously uninfected cohort and the previously infected cohort, respectively. By the end of the study duration, 94.9% of the participants had received two vaccine doses, of which 78.5% had received the BNT162b2 vaccine with a long dosing interval, 8.6% had received the BNT162b2 vaccine with a short dosing interval, and 7.8% had received the ChAdOx1nCoV-19 vaccine.

As the primary outcome, RT-PCR-confirmed SARS-CoV-2 infections occurred in 2,747 participants during follow-up. At 14 days before or after the date of the positive RT-PCR test, 1,673 (61%) reported COVID-19–related symptoms, and 357 participants (13%) also reported a hospital visit. Among 210 cases of SARS-CoV-2 reinfections, although 71 (34%) reported COVID-19–related symptoms, only 18 (9%) of them visited a hospital.

In the cohort of 26,280 previously uninfected participants who received two doses of the BNT162b2 vaccine at a long-dosing interval, a considerably reduced risk of infection was observed over the first six months peaking in the first two months, with adjusted VE between 72% and 92%. However, this immunity waned after six months, reducing protection levels to between 22% and 69%.

The protection offered by two doses of the BNT162b2 vaccine considerably reduced the risk of both asymptomatic and symptomatic SARS-CoV-2 infection in the short term regardless of short or long dosing interval; however, the protection waned after six months. In comparison, two doses of the ChAdOx1nCoV-19 vaccine offered considerably lower immune protection overall. 

Only a few participants in the study cohort remained unvaccinated during the study period, therefore, the authors could study limited cases of infection-acquired immunity in unvaccinated individuals for the long term. Consistent with previous findings, they observed that infection-acquired immunity offered better protection than vaccine-acquired immunity. Although the authors observed an additional benefit of vaccination in previously infected participants, they did not support the notion that both types of immunity were equivalent or vaccine-acquired immunity was superior. 

Importantly, the authors stated that until the threshold for protective antibody titers against SARS-CoV-2 infection is not established, it will remain challenging to accurately estimate how much vaccine-induced immunity is adequate to prevent reinfection at an individual level.

Conclusion 

While some previous studies have suggested that immune protection conferred by primary infection could last for up to 61 months, others have shown its persistence from five to 12 months. Because of the limited length of follow-up, the current study showed that it lasts for up to a year and then begins to wane. Overall, individuals who received one or two vaccine doses after a primary infection were the most protected against COVID-19.

The authors recommended a booster vaccination strategy to avert the adverse effects of waning immunity, particularly in double-vaccinated, previously uninfected persons; additionally, to effectively reduce reinfections and transmission in the ongoing response to COVID-19.