For more information: www.cdc.gov/COVID19

Work Group interpretations of data 

ACIP COVID-19 Vaccines

Sara Oliver MD, MSPH

ACIP Meeting

January 27, 2021
Clinical Trial Data:

AstraZeneca
 Neutralizing antibodies and binding antibodies measured in participants after 

1 dose and 2-dose series

 Responses similar to convalescent sera comparison

 Th1 biased T-cell response 

 5x1010 dose (2 doses, 28 days apart) selected for US Phase III clinical trials

Immunogenicity Information Reviewed by Work Group

AZD1222 (AstraZeneca) 

Nonreplicating Adenovirus Vector Vaccine 3
 Phase I/II studies

–

–

–

–

–

–

–

–

–

Local and systemic symptoms mild to moderate in severity 

Injection site pain, feeling feverish, muscle ache and headache most common symptoms reported 

Reactogenicity symptoms lower after second dose (small numbers) and in older adults

No vaccine-related serious adverse events (SAEs) reported 

 Global Phase III studies

Similar to results from Phase I/II studies

Reactogenicity symptoms milder and reported less frequently after second dose and in adults 

≥65 years of age

 Clinical Hold/Safety Pause

Study paused due to report of transverse myelitis in the UK

FDA reviewed neurologic events in all trials

Study allowed to be resumed with changes, including independent expert neurology panel 

Safety Information Reviewed by Work Group

AZD1222 (AstraZeneca) 

Nonreplicating Adenovirus Vector Vaccine 4
 Preliminary data from interim global efficacy analysis reviewed 

–

–

–

–

~11,000 participants in UK/Brazil interim analysis

Several dose regimens and inter-dose intervals included in interim analysis

 VE estimate for SD/SD regimen: 62.1% (41.0-75.7%)

Estimate for dose/schedule that is currently being studied in US Phase III trials (SD/SD)

 Pooled VE estimate: 70.4% (54.8-80.6%)

Estimate includes individuals with a lower dose (LD) as the first dose, and standard 

dose (SD) as the second dose

Efficacy Information Reviewed by Work Group

AZD1222 (AstraZeneca) 

Nonreplicating Adenovirus Vector Vaccine 5
 Phase III trial in the US is ongoing and will be the primary basis for EUA application

 Over 32,000 people enrolled in Phase III efficacy trials

 Primary endpoint: symptomatic, virologically confirmed COVID-19 disease

 Targets to enroll diverse populations:

–

–

–

Race and ethnicity

Age (<65 years and ≥65 years of age)

Underlying medical conditions 

Plans for U.S. Phase III Trials

6
 Phase I/II data from the vaccines show induction of binding and neutralizing 

antibodies as well as T-cell responses, favorable safety/reactogenicity profile, 

supporting advance to Phase III trials

 Safety pauses are expected with large clinical trials, indicate the process is 

working appropriately

–

–

Transparency around safety pause and resolution is critical

 Await results of US Phase III data for EUA application 

2 doses of 5x1010 dose, 28 days apart 

Work Group Interpretation 

AZD1222 (AstraZeneca)

7
COVID-19 and children
 While overall burden of COVID-19 may be lower among children, preventable 

infections, hospitalizations, long-term sequelae and deaths are an important 

public health problem

 Clinical trials to evaluate safety and immunogenicity of COVID-19 vaccines 

in children are essential

 Given the disparities noted among COVID-19 cases among children and MIS-C, 

will be crucial for pediatric clinical trials to enroll a diverse population

Work Group interpretation

COVID-19 and children

9
Vaccine Effectiveness Studies
Work Group interpretation

COVID-19 vaccine effectiveness studies 

11

 “Real-world” vaccine effectiveness studies are needed for a variety of 

populations, ages, and conditions

 Diverse trial designs will be important to address variety of questions

 Isolates obtained through VE platforms can help address concerns around 

SARS-CoV-2 variants 
SARS-CoV-2 variants
 In fall of 2020, several SARS-CoV-2 variants emerged, with changes in receptorbinding domain of spike protein – confer increased transmissibility

SARS-CoV-2 Variants

Emerging SARS-CoV-2 Variants | CDC

Amino acid change in 

spike protein

United Kingdom

(B.1.1.7)

South Africa

(20H/501Y.V2 or B.1.351)

Brazil

(P.1)

No. of spike changes 8 10 12

N501Y

E484K

K417T/N
 In fall of 2020, several SARS-CoV-2 variants emerged, with changes in receptorbinding domain of spike protein – confer increased transmissibility

SARS-CoV-2 Variants

Emerging SARS-CoV-2 Variants | CDC

Amino acid change in 

spike protein

United Kingdom

(B.1.1.7)

South Africa

(20H/501Y.V2 or B.1.351)

Brazil

(P.1)

No. of spike changes 8 10 12

N501Y

E484K

K417T/N

Does the variant have the ability to evade vaccine -induced immunity?
Following vaccination, study participant sera (n=8–20) tested in neutralization assays:

 Pfizer BioNTech COVID-19 vaccine: 

–

–

–

–

–

Several studies have demonstrated equivalent neutralizing titers against a panel of 19 individual 

SARS-CoV-2 spike variants1 and N501Y (variant)2 compared to wildtype virus

Reductions to neutralizing titers have been noted against the B.1.1.7 (UK) variant (all mutations):

• 1.3-fold average reduction3

• 3.9-fold median reduction4

One study with modest reduction (<3-fold) for some with neutralization against certain SARS-CoV-2 spike 

mutations from B.1.351 (South African) and P.1 (Brazil) variants: E484K and K417N:E484K:N501Y5

 Moderna COVID-19 Vaccine:

One study with modest reduction (<3-fold) for some with neutralization against certain SARS-CoV-2 spike 

mutations from B.1.351 (South African) and P.1 (Brazil) variants: E484K and K417N:E484K:N501Y5

Another study with no significant impact on neutralizing titers against B.1.1.7 (UK) variant, but 6-fold 

reduction for B.1.351 (South African) variant6

SARS-CoV-2 Variants: Implications for vaccination

1. Sahin et al. medRxiv preprint (Dec 11, 2020a); doi: https://doi.org/10.1101/2020.12.09.20245175

2. Xie et al. bioRxiv preprint (Jan 07, 2021) ; doi: https://doi.org/10.1101/2021.01.07.425740

3. Muik et al. bioRxiv preprint (Jan 19, 2021); doi: https://doi.org/10.1101/2021.01.18.426984

4. Collier et al. medRxiv preprint (Jan 20, 2021); doi: https://doi.org/10.1101/2021.01.19.21249840

5. Wang et al. bioRxiv preprint (Jan 15, 2021) ; doi: https://doi.org/10.1101/2021.01.15.426911

6. Wu et al. BioRxiv preprint ((Jan 25, 2021); doi: https://doi.org/10.1101/2021.01.25.427948
 National SARS-CoV-2 Strain Surveillance (“NS3”)

–

–

–

–

–

–

Being scaled to process ~750 samples nationally per week

Allows for characterization of viruses beyond sequencing

 Surveillance in partnership with national reference laboratories

~1,750 samples per week +

 Universities

CDC has contracts with seven universities to conduct genomic surveillance in collaboration with PH agencies

 Sequencing within state and local health departments

Epidemiology and Laboratory Capacity Program supports integrating next-generation sequencing and 

bioinformatics into the U.S. public health system

 The SPHERES consortium

CDC leads a national consortium of ~160 laboratories sequencing SARS-CoV-2 (SPHERES)

 Sequencing of vaccine breakthrough cases

SARS-CoV-2 Variants: Strain Surveillance in the U.S.

Emerging SARS-CoV-2 Variants | CDC
 In most of the studies reviewed, minimal to moderate reduction (1.3–6-fold) in 

neutralization activity for vaccine-immune sera in some persons

–

–

–

–

Implications for ‘real world’ effectiveness unclear- sera from mRNA vaccine recipients had higher 

neutralization activity than COVID-19 convalescent human sera in early phase clinical trials

Limited studies, small numbers

 Evidence quickly evolving, so continued review of data critical

Studies evaluating the full sets of mutation from variants likely more informative than studies of 

single mutations

Studies of vaccine breakthrough cases are planned and may serve as an early waring

 Moderna has announced they are developing a vaccine against B.1.351 (South African) 

variant

Implications and discussion
COVID-19 vaccine dosing and schedules
 mRNA vaccines are recommended for a two-dose series administered 

intramuscularly

–

–

Pfizer-BioNTech: Three weeks apart

Moderna: Four weeks apart

 Persons should not be scheduled to receive the second dose earlier than the 

recommended intervals 

– However, doses administered earlier should not be repeated

 The second dose should be administered as close to the recommended interval as 

possible. However, if it is not feasible to adhere to the recommended interval, the 

second dose of Pfizer-BioNTech and Moderna COVID-19 vaccines may be scheduled for 

administration up to 6 weeks (42 days) after the first dose. 

Dosing and administration

https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
Alternative Dosing/Schedules:

20

 Currently, recommended schedule and doses from Phase III trials where 

safety and high efficacy were demonstrated

 If data become available for alternative schedules or doses, ACIP can review 

data and consider new recommendations

 However, in the absence of additional data to support alternative schedules 

or doses, the current recommendations will remain 
 mRNA vaccines are not interchangeable with each other or other COVID-19 vaccines

–

–

–

Either vaccine series may be used; ACIP does not state a product preference

Every effort should be made to determine which vaccine product was received as the first 

dose

In exceptional situations in which the first-dose vaccine product cannot be determined or is 

no longer available, any available mRNA COVID-19 vaccine may be administered at a 

minimum interval of 28 days between doses

Dosing and administration

https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
 mRNA vaccines should be administered alone, with a minimum interval of 14 days 

before or after administration with any other vaccines

–

–

However, mRNA COVID-19 vaccines and other vaccines may be administered within a 

shorter period in situations where benefits of vaccination are deemed to outweigh the 

potential unknown risks of vaccine coadministration

If mRNA COVID-19 vaccines are administered within 14 days of another vaccine, doses do 

not need to be repeated for either vaccine

Dosing and administration

https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
Next Steps
 Any vote on the use of additional COVID-19 vaccines will take place at an Emergency 

ACIP meeting once FDA has authorized the vaccine and data are reviewed by ACIP, 

including safety and efficacy results from Phase III trials

 Janssen vaccine may have results from Phase III trial within next several weeks 

–

–

Adenovirus 26 (Ad.26) vector vaccine

Current U.S. Phase III trials evaluating a single dose

Next Steps

https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
Adenovirus vector vaccines

Graphic source: https://www.research.ox.ac.uk/Article/2020-07-19-the-oxford-covid-19-vaccine

Chimpanzee adenovirus vector 

 Nonreplicating

 Chimpanzee adenovirus vector circumvents 

preexisting immunity to human adenovirus 

Human adenovirus 26 (Ad.26) vector 

 Nonreplicating

 Used in other vaccines (Ebola vaccine) 

 Ad.26 Ebola vaccine used in broad populations, 

including pregnant women and children

 Previous exposure to the vector could reduce 

effectiveness

Graphic source: https://www.janssen.com/infectious-diseases-and-vaccines/vaccine-technology
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.

Thank you
Efficacy after dose 1

Phase III data 

27

Pfizer-BioNTech COVID-19 vaccine

 Most (98%) recipients received 2 doses of the Pfizer-BioNTech vaccine

 Efficacy of 52.4% (29.5–68.4%) noted between dose 1 and dose 2

 Additional data in UK press statement (not included in submission to FDA or CDC):

–

–

–

–

Cases from day 15-day 21: VE of 89% (52-97%)

Follow-up only until day 21

Moderna COVID-19 vaccine

 Most (97%) recipients received 2 doses of the Moderna vaccine

 Efficacy of 69.5% (43.5–84.5%) noted between dose 1 and dose 2

 Additional data from Moderna Phase III trial: 

Non-randomized sample of persons who only received 1 dose: VE of 92% (66–98%), 

Median follow-up only 28 days
 In fall of 2020, several SARS-CoV-2 variants emerged, notable changes in receptorbinding domain of spike protein – confer higher viral burden, increased infectivity

 Some changes (e.g.,E484K) affect polyclonal/monoclonal antibody neutralization

SARS-CoV-2 Variants

Emerging SARS-CoV-2 Variants | CDC

Amino acid change in 

spike protein

United Kingdom

(B.1.1.7)

South Africa

(20H/501Y.V2 or B.1.351)

Brazil

(P.1)

No. of spike changes 8 10 3

N501Y

E484K

K417T/N