For more information: www.cdc.gov/COVID19

ACIP COVID-19 Vaccines 

Update on Emerging 

SARS-CoV-2 Variants and 

Vaccine Considerations 

CDR Heather Scobie PhD, MPH 

ACIP Meeting 

May 12, 2021 
Background 
 

 

 

 

SARS-CoV-2 Variants 

▪ Multiple SARS-CoV-2 variants circulating globally 

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Viruses constantly change through mutation, so new variants are expected 

After emerging, some disappear; others persist 

▪ CDC and others are studying these variants to understand whether they: 

Spread more easily from person to person 

Cause milder or more severe disease in people 

Detected by available diagnostic tests 

Respond to therapeutics currently used to treat people for COVID-19 

Change effectiveness of COVID-19 vaccines 

https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant.html 
 

 

 

 

 

 

 

 

 

Variant Classifications 

▪ Established in collaboration with the SARS-CoV-2 Interagency Group (SIG) 

▪ Variant of Interest (VOI): Genetic markers associated with changes to receptor 

binding, reduced antibody neutralization, reduced efficacy of treatments, potential 

diagnostic impact, or predicted increase in transmissibility or disease severity 

▪ Variant of Concern (VOC): Evidence of increased transmissibility, more severe 

disease, significant reduction in neutralization by antibodies, reduced effectiveness 

of treatments or vaccines, or diagnostic detection failures 

▪ Variant of High Consequence (VOHC): Clear evidence that prevention measures or 

medical countermeasures have significantly reduced effectiveness [None yet] 

SARS-CoV-2 Variants Classifications & Definitions | CDC 
 

 

 

Variants of Interest 

B.1.526 B.1.526.1 B.1.525 P.2 B.1.617 B.1.617.1 B.1.617.2 B.1.617.3 

First detected New York New York UK/Nigeria Brazil India India India India 

No. of spike 

mutations 

3-7 6-8 8 3-4 3 7-8 9-10 7 

Receptor 

binding domain 

mutations 

(S477N*) 

(E484K*) 

L452R E484K E484K L452R 

E484Q 

L452R 

E484Q 

L452R 

T478K 

L452R 

E484Q 

Attributes • Reduced • Potential reduced • Potential • Potential • Potential reduced antibody 

antibody antibody efficacy reduced reduced efficacy 

efficacy • Potential reduced antibody antibody • Potential reduced neutralization 

• Reduced neutralization by efficacy efficacy by vaccine sera 

neutralization vaccine sera • Reduced • Reduced 

convalescent neutraliza- neutralizaor vaccine sera tion by tion by 

vaccine vaccine 

sera sera 

SARS-CoV-2 Variants Classifications & Definitions | CDC (*) = detected in some sequences but not all 
 

 

 

Variants of Interest 

B.1.526 B.1.526.1 B.1.525 P.2 B.1.617 B.1.617.1 B.1.617.2 B.1.617.3 

First detected New York New York UK/Nigeria Brazil India India India India 

No. of spike 

mutations 

3-7 6-8 8 3-4 3 7-8 9-10 7 

Receptor 

binding domain 

mutations 

(S477N*) 

(E484K*) 

L452R E484K E484K L452R 

E484Q 

L452R 

E484Q 

L452R 

T478K 

L452R 

E484Q 

Attributes • Reduced • Potential reduced • Potential • Potential • Potential reduced antibody 

antibody antibody efficacy reduced reduced efficacy 

efficacy • Potential reduced antibody antibody • Potential reduced neutralization 

• Reduced neutralization by efficacy efficacy by vaccine sera 

neutralization vaccine sera • Reduced • Reduced 

convalescent neutraliza- neutralizaor vaccine sera tion by tion by 

vaccine vaccine 

sera sera 

SARS-CoV-2 Variants Classifications & Definitions | CDC (*) = detected in some sequences but not all 
 

 

 

Variants of Interest 

B.1.526 B.1.526.1 B.1.525 P.2 B.1.617 B.1.617.1 B.1.617.2 B.1.617.3 

First detected New York New York UK/Nigeria Brazil India India India India 

No. of spike 3-7 6-8 8 3-4 3 7-8 9-10 

mutations 

Receptor 

binding domain 

mutations 

(S477N*) 

(E484K*) 

L452R E484K E484K L452R 

E484Q 

L452R 

E484Q 

L452R 

T478K 

L452R 

E484Q 

Attributes • Reduced • Potential reduced • Potential • Potential • Potential reduced antibody 

antibody antibody efficacy reduced reduced efficacy 

efficacy • Potential reduced antibody antibody • Potential reduced neutralization 

• Reduced neutralization by efficacy efficacy by vaccine sera 

neutralization vaccine sera • Reduced • Reduced 

convalescent neutraliza- neutralizaor vaccine sera tion by tion by 

vaccine vaccine 

sera sera 

7 

SARS-CoV-2 Variants Classifications & Definitions | CDC (*) = detected in some sequences but not all 
 

 

Variants of Concern 

B.1.1.7 B.1.351 P.1 B.1.427 B.1.429 

First detected United Kingdom South Africa Japan / Brazil California California 

No. of spike 

mutations 

10-13 10 11 4 4 

Receptor 

binding domain 

mutations 

N501Y K417N 

E484K 

N501Y 

K417T 

E484K 

N501Y 

L452R L452R 

Attributes • 50% increased 

transmission 

• Minimal impact 

on neutralization 

by antibody 

therapies, 

convalescent or 

vaccine sera 

• 50% increased 

transmission 

• Reduced efficacy 

of some antibodies 

• Reduced 

neutralization 

by convalescent or 

vaccine sera 

• Reduced 

efficacy of some 

antibodies 

• Reduced 

neutralization 

by convalescent 

or vaccine sera 

• 20% increased 

transmission 

• Modest decrease 

in efficacy of some 

antibodies 

• Reduced 

neutralization 

by convalescent or 

vaccine sera 

• 20% increased 

transmission 

• Modest decrease in 

efficacy of some 

antibodies 

• Reduced 

neutralization 

by convalescent or 

vaccine sera 

SARS-CoV-2 Variants Classifications & Definitions | CDC 
 

 

Variants of Concern 

B.1.1.7 B.1.351 P.1 B.1.427 B.1.429 

First detected United Kingdom South Africa Japan / Brazil California California 

No. of spike 

mutations 

Attributes 

10-13 

• 50% increased 

transmission 

• Minimal impact 

on neutralization 

by antibody 

therapies, 

convalescent or 

vaccine sera 

10 

• 50% increased 

transmission 

• Reduced efficacy 

of some antibodies 

• Reduced 

neutralization 

by convalescent or 

vaccine sera 

11 

efficacy of some 

antibodies 

• Reduced 

neutralization 

by convalescent 

or vaccine sera 

4 

• 20% increased 

transmission 

• Modest decrease 

in efficacy of some 

antibodies 

• Reduced 

neutralization 

by convalescent or 

vaccine sera 

4 

• 20% increased 

transmission 

• Modest decrease in 

efficacy of some 

antibodies 

• Reduced 

neutralization 

by convalescent or 

vaccine sera 

Receptor 

binding domain 

mutations 

N501Y K417N 

E484K 

N501Y 

K417T 

E484K 

N501Y 

L452R L452R 

• Reduced 

SARS-CoV-2 Variants Classifications & Definitions | CDC 
 

 

Variants of Concern 

B.1.1.7 B.1.351 P.1 B.1.427 B.1.429 

First detected United Kingdom South Africa Japan / Brazil California California 

No. of spike 

mutations 

10-13 10 11 4 4 

Receptor 

binding domain 

mutations 

N501Y K417N 

E484K 

N501Y 

K417T 

E484K 

N501Y 

L452R L452R 

Attributes • 50% increased 

transmission 

• Minimal impact 

on neutralization 

by antibody 

therapies, 

convalescent or 

vaccine sera 

• 50% increased 

transmission 

• Reduced efficacy 

of some antibodies 

• Reduced 

neutralization 

by convalescent or 

vaccine sera 

• Reduced 

efficacy of some 

antibodies 

• Reduced 

neutralization 

by convalescent 

or vaccine sera 

• 20% increased 

transmission 

• Modest decrease 

in efficacy of some 

antibodies 

• Reduced 

neutralization 

by convalescent or 

vaccine sera 

• 20% increased 

transmission 

• Modest decrease in 

efficacy of some 

antibodies 

• Reduced 

neutralization 

by convalescent or 

vaccine sera 

SARS-CoV-2 Variants Classifications & Definitions | CDC 
Genomic Surveillance & 

Epidemiology of SARS-CoV-2 Variants 
U.S. Sequences Available in Public Repositories 

 

 

 

Data 

collection 

ongoing 

6%-9% of SARSCoV-2 positive 

cases sequenced 

weekly 

CDC COVID Data Tracker 

As of 5/11/21 NCBI=National Center for Biotechnology Information; GISAID, a global initiative maintaining a repository of viral sequencing data 
 

 

 

 

 

 

 

Estimates for April 25-May 8, 2021 

National SARS-CoV-2 Variant Proportions, United States 

January 17 – May 8, 2021 with NOWCAST 

Collection Date, 2-weeks ending 

Percent of Viral Lineages 

VOC / VOI 

B.1.1.7 72% 

B.1.427/B.1.429 1% 

P.1 6% 

B.1.351 <1% 

B.1.526 7% 

B.1.526.1 3% 

B.1.617.2 3% 

CDC COVID Data Tracker As of 5/11/21; VOC=Variant of Concern; VOI=Variant of Interest 
Regional SARS-CoV-2 Variant Proportions 

April 25 – May 8, 2021 with NOWCAST 

Lineage 

 

 

CDC COVID Data Tracker As of 5/11/21; VOC=Variant of Concern; VOI=Variant of Interest 
Vaccine Effectiveness 

Against SARS-CoV-2 Variants 
Figure Source: Altman et al (2021): https://science.sciencemag.org/content/371/6534/1103 

Earle et al. medRxiv preprint (March 20, 2021): https://doi.org/10.1101/2021.03.17.20200246 

 

 

 

 

 

 

 

 

Vaccine-Induced Antibody Protection and Variants 

▪ Robust correlation between 

vaccine efficacy (VE) versus: Antibodies –

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Neutralizing titer (ρ= 0.79)

Binding antibody titer (ρ = 0.93)

▪ Correlate of protection, or 

threshold that protects against 

SARS-CoV-2, not yet determined 

▪ Variants result in reduced 

protective antibody levels 

Lower VE and increased 

breakthrough infection? E484K + future 

Shorter duration of immunity? escape mutants? 
Vaccine-Induced Antibody Protection and Variants 

▪ Robust correlation between 

vaccine efficacy (VE) versus: 

– Neutralizing titer (ρ= 0.79)

– Binding antibody titer (ρ = 0.93)

▪ Correlate of protection, or 

threshold that protects against 

SARS-CoV-2, not yet determined 

▪ Variants result in reduced 

protective antibody levels 

– Lower VE and increased 

breakthrough infection? 

– Shorter duration of immunity? 

Figure Source: Altman et al (2021): https://science.sciencemag.org/content/371/6534/1103 

Earle et al. medRxiv preprint (March 20, 2021): https://doi.org/10.1101/2021.03.17.20200246 

Antibodies 

E484K + future 

escape mutants? 

 

 

 

 

 

 

 

 
Vaccine-Induced Antibody Protection and Variants 

▪ Robust correlation between 

vaccine efficacy (VE) versus: 

– Neutralizing titer (ρ= 0.79)

– Binding antibody titer (ρ = 0.93)

▪ Correlate of protection, or 

threshold that protects against 

SARS-CoV-2, not yet determined 

▪ Variants result in reduced 

protective antibody levels 

– Lower VE and increased 

breakthrough infection? 

– Shorter duration of immunity? 

Figure Source: Altman et al (2021): https://science.sciencemag.org/content/371/6534/1103 

Earle et al. medRxiv preprint (March 20, 2021): https://doi.org/10.1101/2021.03.17.20200246 

Antibodies 

E484K + future 

escape mutants? 

 

 

 

 

 

 

 

 
 

 

Reduced Neutralization Activity of Vaccine Sera 

Relative to Wildtype/Dominant Strain, by Study (n=31) 

B.1.1.7 B.1.351 P.1 P.2 B.1.1.7 B.1.617 B.1617.1 B.1.429 B.1.526 B.1.526 

1

10

100

Fold reduction 

mRNA 

Novavax 

AstraZeneca 

Studies by 

vaccine 

No effect = 

UK SA Brazil Brazil +E484K India India CA NY +E484K 
 

 

 

 

 

 

Discussion of Lab Studies 

▪ Largest impacts: B.1.351 (SA) > P.1 (Brazil) > B.1.1.7 (UK), B.1.427/B.429 (CA)

▪ Difficult to estimate how results might translate to clinical protection 

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Neutralizing antibodies in sera from mRNA vaccine recipients higher than COVID-19 

convalescent sera 

▪ Variation in results may be explained by different experimental conditions 

Neutralization assays — replicating & nonreplicating pseudovirus vs. SARS-CoV-2 

Sera — time post-vaccination, or population (e.g., age, COVID-19 history) 

Use of limited or full sets of spike mutations vs. clinical isolates of variants 

▪ Limitation for all studies — small sample sizes and lack generalizability 

Almost half of studies are preprints, not yet peer-reviewed 
 

 

 

 

 

 

 

 

Vaccine Efficacy or Effectiveness (VE) Against Variants 

Vaccine Study type VE 

Pfizer Post-EUA • 90% against B.1.1.7 in Qatar* 

• 75% against B.1.351 in Qatar 

Janssen Pre-EUA • 74% in U.S. 

• 66% in Brazil (69% of cases from P.2) 

• 52% in S. Africa (95% of cases from B.1.351) 

Novavax Pre-EUA • 96% against non-B.1.1.7 in UK 

• 86% against B.1.1.7 in UK 

Pre-EUA • 51% against B.1.351 in S. Africa 

AstraZeneca Pre-EUA • 84% against non-B.1.1.7 in UK 

• 75% against B.1.1.7 in UK 

Pre-EUA • 10% against B.1.351 in South Africa** 

 

 

 

 

 

* >85% in UK & Israel (predominate B.1.1.7): https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html 

Abu-Radad and Butt. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants | NEJM 

https://www.fda.gov/media/146217/download 

Novavax.: https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3 

Shinde et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant | NEJM 

Madhi et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant | NEJM 

Emary et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7)- The Lancet **mild/moderate illness 
 

 

 

 

 

 

 

 

 

 

 

Vaccine Efficacy or Effectiveness (VE) Against Variants 

Vaccine Study type VE 

Pfizer Post-EUA • 90% against B.1.1.7 in Qatar* 

• 75% against B.1.351 in Qatar 

100% for severe/ 

critical disease 

Janssen Pre-EUA • 74% in U.S. 

• 66% in Brazil 

• 52% in S. Africa 

73-82% for severe/critical 

disease in each country 

Novavax Pre-EUA • 96% against non-B.1.1.7 in UK 

• 86% against B.1.1.7 in UK 

Pre-EUA • 51% against B.1.351 in S. Africa 

AstraZeneca Pre-EUA • 84% against non-B.1.1.7 in UK 

• 75% against B.1.1.7 in UK 

Pre-EUA • 10% against B.1.351 in South Africa* 

* >85% in UK & Israel (predominate B.1.1.7): https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html 

Abu-Radad and Butt. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants | NEJM 

https://www.fda.gov/media/146217/download 

Novavax.: https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3 

Shinde et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant | NEJM 

Madhi et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant | NEJM 

Emary et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7):- The Lancet **mild/moderate illness 
 

 

 

 

 

 

 

 

Investigating COVID-19 Vaccine Breakthrough Cases 

▪ Despite high vaccine efficacy, vaccine breakthrough cases* expected 

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Some will be caused by variants, even if vaccine has similar effectiveness against variants 

▪ Among 95 million fully vaccinated in U.S., 9,245 breakthrough infections** 

reported by state & territorial health departments to passive surveillance 

Case investigation and whole genome sequencing to identify variants 

▪ Starting soon – CDC project with Emerging Infections Program sites on 

frequency of SARS-CoV-2 variants among vaccinated and unvaccinated people 

* Vaccine breakthrough case: Person with SARS-CoV-2 RNA or antigen detected in respiratory specimen collected 

≥14 days after completing primary series of an FDA-authorized COVID-19 vaccine 

** COVID-19 Breakthrough Case Investigations and Reporting | CDC as of 4/26/21 

Tehran et al. https://www.cdc.gov/mmwr/volumes/70/wr/mm7017e1.htm 
 

 

 

 

 

 

 

 

 

 

Do SARS-CoV-2 Variants Cause More Breakthrough Cases? 

▪ One preprint study from Israel assessed variants of concern (VOC) in infections 

of Pfizer-vaccinated cases vs. unvaccinated matched controls 

▪ Context: B.1.1.7 dominant strain; B.1.351 <1% of all specimens 

▪ At least a week after 2nd dose — matched OR = 8.0 for B.1.351 

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Among 149 pairs, 8 vaccinated and 1 unvaccinated persons had B.1.351 

▪ 2 weeks after 1st dose to 1 week after 2nd dose — matched OR = 2.6 for B.1.1.7 

Among 245 pairs, 221 vaccinated and 205 unvaccinated persons had B.1.1.7 

▪ Conclusion: breakthrough infection more frequent with VOCs 

▪ Limitations: not yet peer-reviewed, small sample sizes (especially B.1.351) 

Kustin et al. MedRxiv preprint (16 April 2021): https://www.medrxiv.org/content/10.1101/2021.04.06.21254882v2 
 

 

 

 

Summary of Preliminary Data: Implications of SARSCoV-2 Variants of Concern on Vaccine Effectiveness 

▪ B.1.1.7 

– Exponential increase in prevalence in United States 

– Minimal impact on VE; attention needed for additional substitutions in 

receptor binding domain (RBD), such as E484K 

▪ B.1.351 

– Currently low prevalence in United States 

– Moderate impact on VE for some vaccines, though may still provide 

protection against severe disease 

▪ P.1 

– Increasing prevalence in United States; same 3 RBD mutations as B.1.351 

– Additional data needed on potential impact on VE 
 

 

 

 

 

 

 

Boosters and Second-Generation Vaccines Against 

SARS-CoV-2 Variants 

▪ Manufacturers launching booster studies of current vaccines and/or 

developing second-generation vaccines against B.1.351 

▪ Moderna — preliminary phase 2 results of single 50 μg booster of authorized 

(mRNA-1273) and variant-specific vaccine (mRNA-1273.351) 

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6-8 months after primary series (pre-booster), low/undetectable neutralizing antibody 

titers for B.1.351 and P.1, but titers against wild-type still likely protective 

Both vaccines — acceptable safety; boosted immunity to all types (wild-type, B.1.351, P.1) 

mRNA-1273.351 booster more effective than mRNA-1273 at neutralizing B.1.351 

In progress — bivalent vaccine with 1:1 mix of original & variant vaccine (mRNA-1273.211) 

Wu et al. medRxiv preprint (May 6, 2021): https://doi.org/10.1101/2021.05.05.21256716 

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-initial-booster-data-against-sars-cov/ 

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-initiate-study-part-broad-development 
 

 

 

 

 

 

Updates to Vaccines to Address SARS-CoV-2 Variants 

▪ Periodic update of SARS-CoV-2 vaccines likely needed 

▪ FDA defined data needed to support EUA amendment for a vaccine 

addressing emerging SARS-CoV-2 variants — immunogenicity studies 

▪ U.S. SIG* developing an evaluation and risk assessment framework 

– Evidence needed to recommend whether modified vaccine needed 

▪ WHO has role in global coordination, developing risk assessment framework 

*SARS-CoV-2 Interagency Group (SIG) 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-vaccines-prevent-covid-19 
 

 

 

 

 

 

Variants: Implications for Vaccine Policy 

▪ Current prevention measures and authorized vaccines offer protection 

against SARS-CoV-2 variants 

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Efforts needed to increase uptake 

▪ Continue to monitor evidence: 

Emergence and spread of SARS-CoV-2 variants 

Vaccine effectiveness 

Breakthrough infections in vaccinated or previously infected persons 

Ability of postvaccination serum to neutralize emerging variant viruses 

▪ ACIP will review evidence submitted for any next generation vaccines 
 

 

Acknowledgements 

▪ Lab Task Force 

– Vivien Dugan 

– Nicole Paterson 

– Alison Laufer Halpin 

– Sarah Talarico 

– David Wentworth 

– Summer Galloway 

▪ Epi Task Force 

– Adam MacNeil 

– Prabasaj Paul 

▪ Vaccine Task Force (VTF) 

– Marc Fischer 

– Leisha Nolen 

– Sara Oliver 

– Steve Hadler 

– Julia Gargano 

– ACIP WG Team 

▪ Division of Viral Diseases 

– Natalie Thornburg 

– Ben Silk 
 

 

 

 

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.