Longitudinal dynamics of SARS-CoV-2-specific cellular and humoral immunity after natural infection or BNT162b2 vaccination

Abstract

The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations.

Decline of Humoral and Cellular Immune Responses Against SARS-CoV-2 6 Months After Full BNT162b2 Vaccination in Hospital Healthcare Workers

“…The short lifetime of these cells could explain the decline of IFN-γ responses over time observed in our study. However, this decline is consistent with the recent reports suggesting that spike-specific CD4+ T cells are downregulated at 3 and 6 months following vaccination ( 14 , 28 , 29 , 50 , 51 ) but contradict an interesting report suggesting that SARS-CoV-2–specific memory CD4+ T cells, based on the co-expression of CD200 and CD40L among CD45RA-, were relatively stable from 3 to 6 months after mRNA vaccination ( 52 ).…”

Overview of Anti-SARS-CoV-2 Immune Response Six Months after BNT162b2 mRNA Vaccine

“…In this study, the dynamic of the immune response six months after the BNT162b2 mRNA vaccine was analyzed. There are several articles in the scientific literature regarding the immunity after SARS-CoV-2 natural infection [15][16][17][18][19] and on the duration of the immune response after vaccination [4,9,10,20,21]. Here, we assessed the antibody response of 178 HCWs without any history of SARS-CoV-2 infection by chemiluminescent and microneutralization assays 10 days, 1, 3, and 6 months after two doses of the BNT162b2 mRNA vaccine.…”

“…However, on the basis of published results, 10-22% of people immunized against COVID-19, showing a steady decline of the humoral response [5], could present a major risk of breakthrough infection, particularly with variants [6]. Many studies have been conducted on the duration of immunity after natural infection by SARS-CoV-2 [7], and results have been produced concerning the persistence of the antibody response over time and the durability of the cell-mediated immune response, in particular memory B and T cells, after two doses of vaccine [6,[8][9][10].…”

Review of Immunologic Manifestations of COVID-19 Infection and Vaccination

“…Growing evidence links the type and temper of the host immune response to SARS-CoV-2 infection with the severity of illness experienced by those infected. 17 , 18 A study by Almendro-Vasquez et al compared the humoral and cellular responses to COVID-19 infection among patients who experienced a range of symptoms from mild to severe, both in the acute setting, as well as 4-7 months following recovery. 18 Patients with mild infection were well enough to convalesce at home and experienced minimal symptoms, while those with moderate disease were hospitalized, required oxygen, or had non-severe ARDS.…”

“… 17 , 18 A study by Almendro-Vasquez et al compared the humoral and cellular responses to COVID-19 infection among patients who experienced a range of symptoms from mild to severe, both in the acute setting, as well as 4-7 months following recovery. 18 Patients with mild infection were well enough to convalesce at home and experienced minimal symptoms, while those with moderate disease were hospitalized, required oxygen, or had non-severe ARDS. Comparatively, severe infection was characterized by admission to the ICU, a P:F ratio of <200, or death from COVID-19.…”