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





Formulation Efficacy against


infection (phase III


Effectiveness (post


Antibody responses

in humans

T cell responses in humans
BNT162b2 mRNA


(30 μg mRNA,

2 doses, 21 days


mRNA-lipid nanoparticle


full-length S

protein, modified

by two proline

mutations to

lock protein in

the pre-fusion


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


infection: 94–96%

(2 doses) and

46–80% (1 dose)

Any infection:

86–92% (2 doses)

and 46–72% (1 dose)



87% (2 doses) and

71–85% (1 dose)



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



(100 μg mRNA,

2 doses, 28 days


mRNA- lipid

nanoparticle encoding

full- length S

protein, modified

by two proline

mutations to

lock protein in

the pre- fusion


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




of Oxford/

Astra- Zeneca)

(2.5–5 × 1010

viral particles,

2 doses, ≥28 days



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


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


(Janssen) (5 × 1010

viral particles,

1 dose


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


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