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. 2022 Aug 1;5(8):e2226335.
doi: 10.1001/jamanetworkopen.2022.26335.

Durability of Heterologous and Homologous COVID-19 Vaccine Boosts

C Sabrina Tan  1 , Ai-Ris Y Collier  1 , Jingyou Yu  1 , Jinyan Liu  1 , Abishek Chandrashekar  1 , Katherine McMahan  1 , Catherine Jacob-Dolan  1 , Xuan He  1 , Vicky Roy  2 , Blake M Hauser  2 , Jennifer E Munt  3 , Michael L Mallory  3 , Melissa Mattocks  3 , John M Powers  3 , Rita M Meganck  3 , Marjorie Rowe  1 , Rachel Hemond  1 , Esther A Bondzie  1 , Kate H Jaegle  1 , Ralph S Baric  3 , Aaron G Schmidt  2 , Galit Alter  2 , Mathieu Le Gars  4 , Jerald Sadoff  4 , Dan H Barouch  1
Affiliations

Durability of Heterologous and Homologous COVID-19 Vaccine Boosts

C Sabrina Tan et al. JAMA Netw Open. .

Abstract

Importance: Antibody responses elicited by current messenger RNA (mRNA) COVID-19 vaccines decline rapidly and require repeated boosting.

Objective: To evaluate the immunogenicity and durability of heterologous and homologous prime-boost regimens involving the adenovirus vector vaccine Ad26.COV2.S and the mRNA vaccine BNT162b2.

Design, setting, and participants: In this cohort study at a single clinical site in Boston, Massachusetts, 68 individuals who were vaccinated at least 6 months previously with 2 immunizations of BNT162b2 were boosted with either Ad26.COV2.S or BNT162b2. Enrollment of participants occurred from August 12, 2021, to October 25, 2021, and this study involved 4 months of follow-up. Data analysis was performed from November 2021 to February 2022.

Exposures: Participants who were previously vaccinated with BNT162b2 received a boost with either Ad26.COV2.S or BNT162b2.

Main outcomes and measures: Humoral immune responses were assessed by neutralizing, binding, and functional antibody responses for 16 weeks following the boost. CD8+ and CD4+ T-cell responses were evaluated by intracellular cytokine staining assays.

Results: Among 68 participants who were originally vaccinated with BNT162b2 and boosted with Ad26.COV2.S (41 participants; median [range] age, 36 [23-84] years) or BNT162b2 (27 participants; median [range] age, 35 [23-76] years), 56 participants (82%) were female, 7 (10%) were Asian, 4 (6%) were Black, 4 (6%) were Hispanic or Latino, 3 (4%) were more than 1 race, and 53 (78%) were White. Both vaccines were found to be associated with increased humoral and cellular immune responses, including against SARS-CoV-2 variants of concern. BNT162b2 boosting was associated with a rapid increase of Omicron neutralizing antibodies that peaked at a median (IQR) titer of 1018 (699-1646) at week 2 and declined by 6.9-fold to a median (IQR) titer of 148 (95-266) by week 16. Ad26.COV2.S boosting was associated with increased Omicron neutralizing antibodies titers that peaked at a median (IQR) of 859 (467-1838) week 4 and declined by 2.1-fold to a median (IQR) of 403 (208-1130) by week 16.

Conclusions and relevance: Heterologous Ad26.COV2.S boosting was associated with durable humoral and cellular immune responses in individuals who originally received the BNT162b2 vaccine. These data suggest potential benefits of heterologous prime-boost vaccine regimens for SARS-CoV-2.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hauser reported receiving grants from the National Institute of Allergy and Infectious Diseases (F30 AI60908) during the conduct of the study. Dr Baric reported receiving personal fees as a member of the scientific advisory board from Adagio and as a member of the scientific advisory board from VaxArt outside the submitted work; in addition, Dr Baric had a patent for SARS-CoV 2 nLUC indicator viruses issued and used for high-throughput neutralization assays. Dr Alter reported receiving personal fees from Systems Seromyx and Leyden Labs and grants from Sanofi, BioNTech, Pfizer, and Merck outside the submitted work. Dr Sadoff reported receiving grants from the Biomedical Advanced Research and Development Authority (BARDA) (grant to Janssen) both during the conduct of the study and outside the submitted work; in addition, Dr Sadoff had a patent for invention of COVID-19 vaccine pending with all rights assigned to Janssen. Dr Barouch reported receiving personal fees from Pfizer, SQZ, Celsion, Avidea, Laronde, and Meissa; equity from Vector Sciences; and grants from Defense Advanced Research Projects Agency, BARDA, Gates Foundation, Medical Research Council, Henry Jackson Foundation, Pharm-Olam, Gilead, Legend, CureVac, Sanofi, Novavax, Intima, Alkermes, and Zentalis outside the submitted work; in addition, Dr Barouch had a patent for COVID-19 vaccine licensed to Janssen. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Pseudovirus Neutralizing Antibody (NAb) Responses Following Ad26.COV2.S or BNT162b2 Boosting
Pseudovirus NAb titers at weeks 0, 2, 4, and 16 following boosting of BNT162b2 vaccinated individuals with Ad26.COV2.S (A) or BNT162b2 (B) are shown. Pseudovirus NAb titers to SARS-CoV-2 W1/2020 (WA), B.1.617.2 (Delta), B.1.351 (Beta), B.1.1.529 (Omicron BA.1; Om BA1), and B.1.1.529 (Omicron BA.2; Om BA2) are shown. Black bars denote medians. Week 4 depicts a subset of samples and includes samples from weeks 4-10. Participants with positive nucleocapsid (N) serology or a history of breakthrough SARS-CoV-2 infection were excluded. Longitudinal Omicron BA.1 NAb titers (C) and comparison of Omicron BA.1 and BA.2 NAb titers at week 16 (D) are shown. P values reflect 2-tailed Mann-Whitney tests.
Figure 2.
Figure 2.. Live Virus Neutralizing Antibody Responses Following Ad26.COV2.S or BNT162b2 Boosting
Live virus neutralizing antibody (NAb) titers at weeks 0, 2, 4, and 16 following boosting of BNT162b2 vaccinated individuals with Ad26.COV2.S (A) or BNT162b2 (B). Live virus NAb titers to SARS-CoV-2 WA1/2020 (WA), B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1; Om BA1). Black bars denote medians. Longitudinal Omicron BA.1 live virus NAb titers (C) and comparison of Omicron BA.1 live virus NAb titers at week 16 (D) are shown. P value reflects a 2-tailed Mann-Whitney test.
Figure 3.
Figure 3.. Cellular Immune Responses Following Ad26.COV2.S or BNT162b2 Boosting
T-cell responses at weeks 0, 2, and 16 following boosting of BNT162b2 vaccinated individuals with Ad26.COV2.S or BNT162b2. Pooled peptide Spike-specific interferon (IFN)–γ CD8+ T-cell responses (A) and CD4+ T-cell responses (B) by intracellular cytokine staining assays. Ad26.COV2.S (left) and BNT162b2 (right) boosting are displayed on separate plots. C, Comparison of CD8+ and CD4+ T cell responses to WA1/2020 and Omicron BA.1 at week 16 are shown. Black bars denote medians. P values reflect 2-tailed Mann-Whitney tests.
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