This is a summary, written by members of the CITF Secretariat, of:
Sadarangani M, Marchant A, Kollmann TR. Immunological mechanisms of vaccine-induced protection against COVID-19 in humans. Nat Rev Immunol. 2021 Jul 1. doi: 10.1038/s41577-021-00578-z
The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.
Protection from COVID-19 vaccines is likely complex, requiring non-neutralizing antibodies, T cell responses, and innate immune mechanisms, as well as low levels of neutralizing antibodies. CITF Testing Working Party and Immune Science Working Party member Dr. Manish Sadarangani and his team provided an overview on the protective immune responses elicited by currently approved vaccines in Nature Reviews Immunology. They concluded that vaccine monitoring, as well as comprehensive analyses of immunologic data pre- and post-vaccination, are needed to understand the correlates of protection against COVID-19.
Key Points from the review of published data on phase III trials of COVID-19 vaccines:
- The Pfizer and Moderna mRNA vaccines have high efficacy against severe disease of SARS-CoV-2 after a single dose.
- The AstraZeneca vaccine was observed to be about 70% efficacious against symptomatic COVID-19 after a single dose. Antibody production and potent T cell responses were also observed.
- Innate immunity and T cell responses need to be considered to identify a correlate or mechanism of protection against COVID-19.
The authors, along with the World Health Organization, highlight that there is an urgent need to ‘accelerate research to establish correlates of protection from COVID-19 vaccines against infection and disease, including for variants of concern’. Having a comprehensive analysis of immune responses pre- and post-vaccination as well as genetic analyses of infections following vaccination will better inform our understanding of the correlates of protection and help guide vaccine development and licensing for the next generation of vaccines.
Table 1. From the Report: Efficacy and Immune Responses of Currently Approved COVID-19 Vaccines in Canada
| Vaccine
(developer) (dosing regimen) |
Formulation | Efficacy against
symptomatic infection (phase III trials) |
Effectiveness (post
implementation) |
Antibody responses
in humans |
T cell responses in humans |
| BNT162b2 mRNA
(BioNTech/Pfizer) (30 μg mRNA, 2 doses, 21 days apart) |
mRNA-lipid nanoparticle
encoding full-length S protein, modified by two proline mutations to lock protein in the pre-fusion conformation |
95% after 2 doses; 52% after 1 dose, although review of the data suggests efficacy of 93% 14 days after 1 dose, 91% at 6 months post
second dose |
Symptomatic
infection: 94–96% (2 doses) and 46–80% (1 dose) Any infection: 86–92% (2 doses) and 46–72% (1 dose)
Hospitalization: 87% (2 doses) and 71–85% (1 dose)
Asymptomatic infection: 79% (1 dose) and 90% (2 doses) |
S1-binding antibody present
after first dose, responses increased following the second dose; significant NAb was only present after second dose |
Increases in antigen-specific
IFN-γ+ CD4+ and CD8+ T cells after second dose; predominance of IFN-γ and IL-2 secretion, compared with IL-4, suggesting TH1 cell polarization |
| mRNA-1273
(Moderna) (100 μg mRNA, 2 doses, 28 days apart) |
mRNA- lipid
nanoparticle encoding full- length S protein, modified by two proline mutations to lock protein in the pre- fusion conformation |
95% after 2 doses; 92% after 1 dose | Symptomatic
infection: 90% (2 doses) and 80% (1 dose) |
S-binding antibody detected
14 days after first dose, levels increased slightly by 28 days, with marked increase after second dose; minimal NAb present after first dose, peak at 14 days after second dose |
Significant increases in
CD4+ T cells secreting TH1 type cytokines (TNF > IL-2 > IFN-γ) after second dose, small increases in TNF- secreting and IL-2- secreting cells after first dose; minimal change in TH2 cell responses; low levels of CD8+ responses |
| ChAdOx1
nCoV-19 (University of Oxford/ Astra- Zeneca) (2.5–5 × 1010 viral particles, 2 doses, ≥28 days apart) |
Recombinant,
Replication-deficient simian adenovirus vector expressing the full-length S protein with a tPA leader sequence |
62–67% after
2 doses,76% after 1 dose; 90% in participants who received a low dose followed by a high dose; interval between doses varied with a median of 36-69 days; 81% with ≥12-week interval, 55% with <6-week interval |
Hospitalization:
80–94% after 1 dose |
S-binding antibody present
14 days after first dose, levels increased by 28 days; marked increase after second dose, peak at 14 days after second dose; predominantly IgG3 and IgG1; significant NAb detected after first dose, increased by 14 days after second dose; IgG avidity increased 28–56 days after single dose; peak IgM and IgA responses at day 14 or 28 |
Peak T cell responses
14 days after first dose, but slightly higher responses measured 28 days after second dose; increase in TNF and IFN-γ production by CD4+ T cells at day 14 |
| Ad26.COV2.S
(Janssen) (5 × 1010 viral particles, 1 dose |
Recombinant,
replication- deficient human adenovirus 26 expressing full length S protein with two amino acid changes in S1/S2 junction that delete furin cleavage site and two proline substitutions in hinge region that lock protein in the pre-fusion conformation |
67% after 1 dose | – | S-binding and neutralizing antibody present by 28 days after vaccination in 99% of individuals and antibody levels sustained until at least 84 days post-accination | CD4+ and CD8+ T cell responses present at 14 and 28 days post vaccination, based on presence of CD4+ and CD8+ T cells secreting IFN-γ and/or IL-2 and not
IL-4 or IL-3, suggesting TH1 cell polarization of the CD4+ T cell response |
Table adapted from Sadarangani et al’s paper. NAb: neutralizing antibody