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DMID 21-0012 - Heterologous Platform Boost Study

Mix and Match

Advisory Committee on Immunization Practices

October 21, 2021

Robert L. Atmar, MD representing Mix and Match Study Team 

Baylor College of Medicine
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Disclosures:

The speaker receives grant funding from NIAID/IDCRC as coChair and site PI for the MixNMatch and as an investigator on 

the Moderna and Novavax Phase III studies

Atmar et al. ACIP Oct 21, 2021

Robert L. Atmar, MD

Baylor College of Medicine
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Group Sample 

Size

EUA Vaccine Interval

(weeks)

Delayed Booster 

Vaccination

Strategy Tested

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50 Previously dosed Janssen –

Ad26.COV2-S ≥12 Moderna- mRNA-1273 Same StrainHeterologous platform

2

50 Previously dosed Moderna –

mRNA-1273 ≥12 Moderna- mRNA-1273 Control - Same Strain& platform

3

50 Previously dosed 

Pfizer/BioNTech –BNT162b2 ≥12 Moderna- mRNA-1273 Same StrainSimilar platform

4

50 Previously dosed Janssen –

Ad26.COV2-S ≥12 Janssen – Ad26.COV2.S Control - Same Strain& platform

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50 Previously dosed Moderna –

mRNA-1273 ≥12 Janssen – Ad26.COV2.S Same StrainHeterologous platform

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50 Previously dosed 

Pfizer/BioNTech –BNT162b2 ≥12 Janssen – Ad26.COV2.S Same StrainHeterologous platform

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50 Previously dosed Janssen –

Ad26.COV2-S ≥12 Pfizer/BioNTech –BNT162b2

Same Strain

Heterologous platform

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50 Previously dosed Moderna –

mRNA-1273 ≥12 Pfizer/BioNTechBNT162b2

Same Strain

Similar platform

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50 Previously dosed 

Pfizer/BioNTech –BNT162b2 ≥12 Pfizer/BioNTech –BNT162b2

Control - Same Strain

& platform

Moderna

(100 mcg)

Janssen 

(5x1010 vp)

Pfizer 

(30 mcg)

Booster Vaccination

Study Visits: Days 1, 8 (safety call), 15, 29, Months 3, 6, 12

Blood for immunogenicity studies Atmar et al. ACIP Oct 21, 2021
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Volunteer Characteristics

Atmar et al. ACIP Oct 21, 2021
N = 458

2 Participants 

- Group 4 (n = 1)

- Group 6 (n = 1)

- High N protein antibody (D1)

suggestive of prior infection

1 Participant 

- Group 5 (n = 1)

- Covid-19 Study Day 27

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15.4 wks 18.4 wks 21.5 wks

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Immunogenicity

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Summary of Available Immunogenicity through D15/D29

Duke (Montefiori Lab): PsVN (ID50, ID80 and in IU50/mL, IU80 /mL)

• D614G N=~450 (50/arm)

• VoCs N=60, 20/arm, 10/age group

• Beta, Delta - In process

VRC (McDermott Lab): IgG Antibody Binding

• 4-plex (validated) (AU/mL)

• S-2P (Wa-1 and Beta) N=~450 (~50/arm) (AU/mL)

• S-2P Wa-1: Binding Antibody Units/mL (BAU/mL) (International Standard)

• 10-plex Fit for Purpose (FFP)

• S-2P (Alpha, Beta, Gamma, Delta, Wa-1) (AUC/m)

Atmar et al. ACIP Oct 21, 2021
Immunogenicity of all three boosters - IgG binding Antibody (A-C) and Neutralizing Antibody (D-F)

Through Days 15/29

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Atmar et al. ACIP Oct 21, 2021
All 3 vaccines

IgG Serum Binding Antibody Response to

S-2P-Wa-1 (control), B.1.1.7 (alpha), and B.1.617.2 (delta)

FFP 10-plex ECLIA, by Group and Timepoint 

Results are reported as Area Under Curve (AUC)

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Atmar et al. ACIP Oct 21, 2021
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Safety

Atmar et al. ACIP Oct 21, 2021
• Two SAEs

1. Acute renal failure due to rhabdomyolysis from a fall - Unrelated

30 days after mRNA-1273 vaccination

2. Acute cholecystitis - Unrelated

24 days after Ad26.COV2.S vaccination.

• No pre-specified study-halting rules were met

• No new onset chronic medical conditions occurred (through study D29)

• One related AESI

• Severe vomiting that led to a medically attended visit the day after 

vaccination: Ad26.COV2.S boost

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Atmar et al. ACIP Oct 21, 2021
Unsolicited AEs (deemed related to boost) of any severity grade

• mRNA-1273: 24/154 (15.6%) 

• Ad26.COV2.S: 18/150 (12.0%) 

• BNT162b2: 22/154 (14.3%) 

Most related AEs were Grade 1 or 2 severity

Four related Grade 3 AEs:

• Vomiting in one participant - mRNA-1273 booster group

• Vomiting in one participant - Ad26.COV2.S booster group

• Fatigue in one participant - Ad26.COV2.S booster group

• Insomnia in one participant - Ad26.COV2.S booster group

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Atmar et al. ACIP Oct 21, 2021
Booster Solicited AEs

Local and Systemic 

Reactogenicity –

Through Day 8

13

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Limitations -

• Non-randomized, open label design

• Study not designed to compare between boosts

- Didn’t control for intervals between primary vaccine and boosts

• Correlates of protection are not completely elucidated

• Correlates for severe disease and death are even less well understood

• This is only antibody data

- Cellular immune responses are still being analyzed

• These data represent only early timepoints from the trial

- Vaccines may differ in time to reach peak responses, and may have different 

durability of the responses

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Conclusions -

1. Use of mRNA-1273, Ad26.COV2.S and BNT162b2 as booster vaccines led 

to anamnestic serologic responses in all 3 EUA-dose vaccine groups

2. For a given primary EUA Covid-19 vaccine, heterologous boosts elicited 

similar or higher serologic responses as compared to their respective 

homologous booster responses

3. mRNA vaccines resulted in higher antibody titers in the first 28 days after 

the boost

4. No safety concerns identified

Preprint: https://www.medrxiv.org/content/10.1101/2021.10.10.21264827v2 Atmar et al. ACIP Oct 21, 2021
The “MixNMatch” Study Team

Emory 

University

University of 

Maryland

New York University

University of Rochester

Cincinnati Children's 

Hospital University of 

Pittsburgh

University of Texas Medical 

Branch Baylor College of Medicine

Kaiser Permanente 

Washington Health Research 

Institute

The University of Washington

VRC

Duke University

Clinical Sites

Labs

Fred Hutch / SCHARP

Regulatory, Data and Statistical Centers

Moderna, Inc., Johnson&Johnson/Janssen, Pfizer/BioNTech

FHI360

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Questions?