Why going beyond NAbs
is critical
NAbs measurements do suffice for vaccine immunogenicity assessment; but it might not be sufficient for efficacy assessment.
Recent data shows that cellular immunity is present in convalescent subjects following either mild or severe disease, even in the absence of antibodies, suggesting a critical anti-viral cellular response.
Graph adapted from Long et al. Nat Med 26:1200;2020. Dynamic changes in virus-specific IgG levels in the acute and convalescent phases in patients infected with SARS-CoV-2. See also: Robbiani et al. Nature 584:437;2020. Wang et al. Clin Infect Dis 2020; doi: 10.1093/cid/ciaa1143. Benner et al. J Infect Dis 2020; doi: 10.1093/infdis/jiaa581. Sette, Crotty et al. Cell 183:996;2020.
Robust & specific CD4 & CD8 T-cell responses were observed in most convalescent patients, even in subset of patients who make little or no antibodies.
Graph adapted from Sekine et al. Cell 2020; doi.org/10.1016/j.cell.2020.08.017. Dot plots summarizing the frequencies of the proliferation (CTV-) and functionality (IFNg+) of SARS-CoV-2-specific CD4+ and CD8+ T cells by group, serostatus, and specificity. Each dot represents one donor. The dotted line indicates the cutoff for positive responses. ***p < 0.001. Mann-Whitney U test. See also Peng et al. Nat Immunol 2020 doi:10.1038/s41590-020-0782-6. Sette, Crotty et al. Cell 183:1340;2020. Sette, Crotty et al. Cell 183:996;2020.
This is not surprising given long lived T-cell immunity & short-lived Ab titer was a characteristic of recovered subjects of previous SARS and MERS epidemics. FDA guidance are currently focusing on total IgG and NAbs titer measurement as well as recently Th1/Th2 ratios. However, with a gradually saturating vaccine market, runners-up will have to distinguish their product by further detailing its efficacy. Such advanced immune monitoring is something we specialize in at CellCarta.
Partner with our scientists and investigate cellular immunity using:
- ELISpot for a highly sensitive and quantitative measurement of cytokine secreting cells.
- Intra-cellular cytokine staining by flow cytometry to monitor production of multiple cytokines and specific cellular subpopulations of interest.