Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4–28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7–13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.

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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥6 months after infection. Immunoglobulin G (IgG) to the spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month after symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3 to 5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.

Inflammation and Cancer: Triggers, Mechanisms, and Consequences.

https://backend.orbit.dtu.dk/ws/files/238108460/1_s2.0_S0092867420310084_main.pdf

Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19.

The impact of HBsAg on general and HBV-specific immunity

HBV-specific T cell responses in low replicating inactive carrier patients are independent of Hepatitis B surface antigen load

Transcriptome profiles of NK and T cells associated with immune control in chronic hepatitis B patients treated with pegylated interferon alpha-nucleos(t)ide analogue sequential therapy

Protection offered by COVID-19 vaccines wanes over time, requiring an evaluation of different boosting strategies to revert such a trend and enhance the quantity and quality of Spike-specific humoral and cellular immune responses. These immunological parameters in homologous or heterologous vaccination boosts have thus far been studied for mRNA and ChAdOx1 nCoV-19 vaccines, but knowledge on individuals who received a single dose of Ad26.COV2.S is lacking. We studied Spike-specific humoral and cellular immunity in Ad26.COV2.S vaccinated individuals (n=55) who were either primed with Ad26.COV2.S only (n=13), or boosted with a homologous (Ad26.COV2.S, n=28) or heterologous (BNT162b2, n=14) second dose. We compared our findings with the results found in individuals vaccinated with a single (n=16) or double (n=44) dose of BNT162b2. We observed that a strategy of heterologous vaccination enhanced the quantity and breadth of both, Spike-specific humoral and cellular immunity in Ad26.COV2.S vaccinated. In contrast, the impact of homologous boost was quantitatively minimal in Ad26.COV2.S vaccinated and Spike-specific antibodies and T cells were narrowly focused to the S1 region. Although a direct association between quantity and quality of immunological parameters and in vivo protection has not been demonstrated, the immunological features of Spike-specific humoral and cellular immune responses support the utilization of a heterologous strategy of vaccine boost in individuals who received Ad26.COV2.S vaccination.

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Differential immunogenicity of homologous versus heterologous boost in Ad26.COV2.S vaccine recipients.

Control of hepatitis B virus (HBV) infection requires functional virusspecific T cells, yet clinical management of patients with chronic HBV infection (CHB) relies exclusively on the assessment of virological (HBVDNA, HBsAg) and biochemical (alanine transaminase (ALT)) biomarkers. There is, however, a growing recognition of the necessity to categorise CHB patients based on their profile of HBVspecific immunity. Such immunological biomarkers might guide when to start or stop nucleos(t)ide analogue (NA) therapy, and/or identify patients who would benefit from novel therapeutic strategies designed to modify host–virus interaction by restoring HBVspecific immunity, either directly (therapeutic vaccines or check point inhibitors) or indirectly (antisense nucleotides, siRNA) (figure 1). In Gut, Ferrari and Boni’s group present findings which could potentially help address this unmet clinical need. Their study in treatment naïve CHB patients shows that simple phenotypic analysis of total circulating CD8T cells can predict HBVspecific CD8 T cell response to immunomodulatory compounds. For three decades, we have known that HBVspecific T cell immunity differs between patients with acute and CHB (reviewed in Chisari and Ferrari ). More recent works have shown that HBVspecific T cells recover, even though often only partially, 4 after functional cure. 6 Such data support the idea that restoration of functional HBVspecific T cell immunity can achieve HBV control but fails to take into account a key characteristic of HBVspecific T cells in CHB patients: their extreme heterogeneity. 7–9 Although extremely low levels of HBsAg and HBcrAg can predict superior responsiveness to PDL1 blockade, it is now clear that the HBVspecific T cell response does not preferentially segregate into the classical CHB definitions (ie, immune tolerant, chronic active, asymptomatic carriers), which are based on virological and biochemical profiles. 12 HBsAg quantity is not associated with frequency and/or function of HBVspecific T cells. 13 Levels of transaminases, the other biomarker used to categorise CHB patients, do not correlate with HBVspecific T cell responses; ALT levels are not proportional to HBVspecific T cell frequency both in the periphery and the liver. Indeed, hepatic damage in CHB is primarily caused by inflammatory and necrotic events supported by myeloid and nonantigenspecific CD8T cells. Thus, since virological and clinical biomarkers cannot predict the level of HBVspecific T cell immunity, its direct assessment is necessary. Unfortunately, such assessment is highly complex, and has thus far prevented its application in the clinic. It is therefore of great practical importance that Rossi et al showed that a phenotypic analysis of circulating total CD8T cells, performed by analysing exhaustion (PD1, TOX) and memory (CD127, BCL2) markers, can generate an ‘exhaustion score’ that predicts HBVspecific T cell responsiveness to immunomodulatory therapy. The authors first measured the expression of exhaustion and memory markers in selected core and polymeraseHLAA2 restricted CD8T cells in treatment naïve CHB patients with liver inflammation (HBeAg+ and HBeAg− chronic hepatitis). In line with previously described HBVspecific CD8T cell heterogeneity, they found variable levels of expression among patients. The expression of these markers was then quantified to calculate an exhaustion score (EI, a numeric value of the zstandard medium fluorescent values of PD1, TOX, CD39, CD127, BCl2). The authors found that EI scores of HBcorespecific CD8T cells varied across the cohort. The EI score was independent of viral load and HBsAg quantity but positively correlated with ALT. Importantly, the score was inversely correlated with the ability of HBcorespecific CD8T cells to produce cytokines directly ex vivo. To expand on this observation, the authors measured the capacity of the HBcorespecific CD8T cells to proliferate in vitro after peptidespecific stimulation, either in the presence of antioxidant, polyphenolic or PD1/PDL1 targeting compounds or of a tolllike receptor 8 (TLR8) agonist—all agents proposed to restore exhausted T cell function. The ability of the HBcore CD8T cells to proliferate in vitro in the presence of these

Nina Le Bert

Papers

The impact of HBsAg on general and HBV-specific immunity

HBV-specific T cell responses in low replicating inactive carrier patients are independent of Hepatitis B surface antigen load

Transcriptome profiles of NK and T cells associated with immune control in chronic hepatitis B patients treated with pegylated interferon alpha-nucleos(t)ide analogue sequential therapy

Differential immunogenicity of homologous versus heterologous boost in Ad26.COV2.S vaccine recipients.

Quest for immunological biomarkers in the management of CHB patients