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Article ; Online: Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL.

Chong, Elise A / Kumashie, Kingsley Gideon / Chong, Emeline R / Fabrizio, Joseph / Gupta, Aditi / Svoboda, Jakub / Barta, Stefan K / Walsh, Kristy M / Napier, Ellen B / Lundberg, Rachel K / Nasta, Sunita D / Gerson, James N / Landsburg, Daniel J / Gonzalez, Joyce / Gaano, Andrew / Weirick, Madison E / McAllister, Christopher M / Awofolaju, Moses / John, Gavin N /

The Journal of infectious diseases

2024

Abstract: Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. SARS-CoV-2 vaccines created an opportunity for new insights in ... ...

Abstract	Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. SARS-CoV-2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic mRNA vaccine response in retrospective and prospective cohorts with lymphoma and CLL, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active therapies, but non-response was also common within observation and post-treatment groups. Total IgA and IgM correlated with successful vaccine response. In individuals treated with CART-19, non-response was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to allow individualized vaccine timing.
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiae106
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Article: Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

Goel, Rishi R. / Painter, Mark M. / Lundgreen, Kendall A. / Apostolidis, Sokratis A. / Baxter, Amy E. / Giles, Josephine R. / Mathew, Divij / Pattekar, Ajinkya / Reynaldi, Arnold / Khoury, David S. / Gouma, Sigrid / Hicks, Philip / Dysinger, Sarah / Hicks, Amanda / Sharma, Harsh / Herring, Sarah / Korte, Scott / KC, Wumesh / Oldridge, Derek A. /

Erickson, Rachel I. / Weirick, Madison E. / McAllister, Christopher M. / Awofolaju, Moses / Tanenbaum, Nicole / Dougherty, Jeanette / Long, Sherea / D’Andrea, Kurt / Hamilton, Jacob T. / McLaughlin, Maura / Williams, Justine C. / Adamski, Sharon / Kuthuru, Oliva / Drapeau, Elizabeth M. / Davenport, Miles P. / Hensley, Scott E. / Bates, Paul / Greenplate, Allison R. / Wherry, E. John

Cell. 2022 May 26, v. 185, no. 11

2022

Abstract: We examined antibody and memory B cell responses longitudinally for ∼9–10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve ... ...

Abstract	We examined antibody and memory B cell responses longitudinally for ∼9–10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%–50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently reactivated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA-vaccine-induced immunity over time through 3 or more antigen exposures.
Keywords	B-lymphocytes ; Severe acute respiratory syndrome coronavirus 2 ; antigens ; immunity ; vaccination ; vaccines
Language	English
Dates of publication	2022-0526
Size	p. 1875-1887.e8.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.04.009
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Article ; Online: Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination.

Goel, Rishi R / Apostolidis, Sokratis A / Painter, Mark M / Mathew, Divij / Pattekar, Ajinkya / Kuthuru, Oliva / Gouma, Sigrid / Hicks, Philip / Meng, Wenzhao / Rosenfeld, Aaron M / Dysinger, Sarah / Lundgreen, Kendall A / Kuri-Cervantes, Leticia / Adamski, Sharon / Hicks, Amanda / Korte, Scott / Oldridge, Derek A / Baxter, Amy E / Giles, Josephine R /

Weirick, Madison E / McAllister, Christopher M / Dougherty, Jeanette / Long, Sherea / D'Andrea, Kurt / Hamilton, Jacob T / Betts, Michael R / Luning Prak, Eline T / Bates, Paul / Hensley, Scott E / Greenplate, Allison R / Wherry, E John

Science immunology

2021 Volume 6, Issue 58

Abstract: Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen- ... ...

Abstract	Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting.
MeSH term(s)	Adult ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; B-Lymphocytes/immunology ; COVID-19/immunology ; COVID-19 Vaccines ; Female ; Humans ; Male ; Middle Aged ; RNA, Messenger ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Vaccination ; Vaccines, Synthetic ; Young Adult ; mRNA Vaccines
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; Spike Glycoprotein, Coronavirus ; Vaccines, Synthetic
Language	English
Publishing date	2021-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abi6950
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Article: Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination.

Goel, Rishi R / Apostolidis, Sokratis A / Painter, Mark M / Mathew, Divij / Pattekar, Ajinkya / Kuthuru, Oliva / Gouma, Sigrid / Kuri-Cervantes, Leticia / Meng, Wenzhao / Adamski, Sharon / Baxter, Amy E / Giles, Josephine R / Weirick, Madison E / McAllister, Christopher M / Hicks, Amanda / Korte, Scott / Dougherty, Jeanette / Long, Sherea / D'Andrea, Kurt /

Hamilton, Jacob T / Prak, Eline T Luning / Betts, Michael R / Bates, Paul / Hensley, Scott E / Greenplate, Allison R / Wherry, E John

medRxiv : the preprint server for health sciences

2021

Abstract: Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in ... ...

Abstract	Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naïve subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naïve subjects remains poorly understood. In this study, we evaluated antibody responses and antigen-specific memory B cell responses over time in 33 SARS-CoV2 naïve and 11 SARS-CoV2 recovered subjects. mRNA vaccination induced significant antibody and memory B cell responses against full-length SARS-CoV2 spike protein and the spike receptor binding domain (RBD). SARS-CoV2 naïve individuals benefitted from both doses of mRNA vaccine with additional increases in antibodies and memory B cells following booster immunization. In contrast, SARS-CoV2 recovered individuals had a significant immune response after the first dose with no increase in circulating antibodies or antigen-specific memory B cells after the second dose. Moreover, the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses. The frequency of pre-vaccine antigen-specific memory B cells in SARS-CoV2 recovered individuals strongly correlated with post-vaccine antibody levels, supporting a key role for memory B cells in humoral recall responses to SARS-CoV2. This observation may have relevance for future booster vaccines and for responses to viral variants that partially escape pre-existing antibodies and require new humoral responses to be generated from memory B cells. Finally, post-boost antibody levels were not correlated with post-boost memory responses in SARS-CoV2 naïve individuals, indicating that short-term antibody levels and memory B cells are complementary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.
Language	English
Publishing date	2021-03-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.03.03.21252872
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Article ; Online: Rapid induction of antigen-specific CD4

Painter, Mark M / Mathew, Divij / Goel, Rishi R / Apostolidis, Sokratis A / Pattekar, Ajinkya / Kuthuru, Oliva / Baxter, Amy E / Herati, Ramin S / Oldridge, Derek A / Gouma, Sigrid / Hicks, Philip / Dysinger, Sarah / Lundgreen, Kendall A / Kuri-Cervantes, Leticia / Adamski, Sharon / Hicks, Amanda / Korte, Scott / Giles, Josephine R / Weirick, Madison E /

McAllister, Christopher M / Dougherty, Jeanette / Long, Sherea / D'Andrea, Kurt / Hamilton, Jacob T / Betts, Michael R / Bates, Paul / Hensley, Scott E / Grifoni, Alba / Weiskopf, Daniela / Sette, Alessandro / Greenplate, Allison R / Wherry, E John

Immunity

2021 Volume 54, Issue 9, Page(s) 2133–2142.e3

Abstract: SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior ...

Abstract	SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4
MeSH term(s)	2019-nCoV Vaccine mRNA-1273 ; Adult ; Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; Antigens, CD/metabolism ; Antigens, Differentiation, T-Lymphocyte/metabolism ; BNT162 Vaccine ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/immunology ; COVID-19 Vaccines/immunology ; Female ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Immunization, Secondary ; Immunologic Memory ; Lectins, C-Type/metabolism ; Lymphocyte Activation ; Male ; Middle Aged ; Peptides/immunology ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/immunology ; Th1 Cells/immunology ; Vaccination ; Young Adult
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Antigens, CD ; Antigens, Differentiation, T-Lymphocyte ; CD69 antigen ; COVID-19 Vaccines ; Lectins, C-Type ; Peptides ; Spike Glycoprotein, Coronavirus ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2021-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2021.08.001
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Article: Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

Goel, Rishi R / Painter, Mark M / Lundgreen, Kendall A / Apostolidis, Sokratis A / Baxter, Amy E / Giles, Josephine R / Mathew, Divij / Pattekar, Ajinkya / Reynaldi, Arnold / Khoury, David S / Gouma, Sigrid / Hicks, Philip / Dysinger, Sarah / Hicks, Amanda / Sharma, Harsh / Herring, Sarah / Korte, Scott / Kc, Wumesh / Oldridge, Derek A /

Erickson, Rachel I / Weirick, Madison E / McAllister, Christopher M / Awofolaju, Moses / Tanenbaum, Nicole / Dougherty, Jeanette / Long, Sherea / D'Andrea, Kurt / Hamilton, Jacob T / McLaughlin, Maura / Williams, Justine C / Adamski, Sharon / Kuthuru, Oliva / Drapeau, Elizabeth M / Davenport, Miles P / Hensley, Scott E / Bates, Paul / Greenplate, Allison R / Wherry, E John

bioRxiv : the preprint server for biology

2022

Language	English
Publishing date	2022-02-22
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.02.20.481163
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Article ; Online: Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

Cell

2022 Volume 185, Issue 11, Page(s) 1875–1887.e8

Abstract: We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve ... ...

Abstract	We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%-50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently reactivated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA-vaccine-induced immunity over time through 3 or more antigen exposures.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; RNA, Messenger ; SARS-CoV-2 ; Vaccines, Synthetic ; mRNA Vaccines
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; Vaccines, Synthetic ; mRNA Vaccines
Language	English
Publishing date	2022-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.04.009
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Article ; Online: Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naive and Recovered Individuals Following mRNA Vaccination

Hamilton, Jacob T / Luning Prak, Eline T / Betts, Michael R / Bates, Paul / Hensley, Scott E / Greenplate, Allison R / Wherry, E. John

medRxiv

Abstract	Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naive subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naive subjects remains poorly understood. In this study, we evaluated antibody responses and antigen-specific memory B cell responses over time in 33 SARS-CoV2 naive and 11 SARS-CoV2 recovered subjects. mRNA vaccination induced significant antibody and memory B cell responses against full-length SARS-CoV2 spike protein and the spike receptor binding domain (RBD). SARS-CoV2 naive individuals benefitted from both doses of mRNA vaccine with additional increases in antibodies and memory B cells following booster immunization. In contrast, SARS-CoV2 recovered individuals had a significant immune response after the first dose with no increase in circulating antibodies or antigen-specific memory B cells after the second dose. Moreover, the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses. The frequency of pre-vaccine antigen-specific memory B cells in SARS-CoV2 recovered individuals strongly correlated with post-vaccine antibody levels, supporting a key role for memory B cells in humoral recall responses to SARS-CoV2. This observation may have relevance for future booster vaccines and for responses to viral variants that partially escape pre-existing antibodies and require new humoral responses to be generated from memory B cells. Finally, post-boost antibody levels were not correlated with post-boost memory responses in SARS-CoV2 naive individuals, indicating that short-term antibody levels and memory B cells are complementary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.
Keywords	covid19
Language	English
Publishing date	2021-03-06
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.03.21252872
Database	COVID19

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Article ; Online: Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination

Goel, Rishi R. / Apostolidis, Sokratis A. / Painter, Mark M. / Mathew, Divij / Pattekar, Ajinkya / Kuthuru, Oliva / Gouma, Sigrid / Kuri-Cervantes, Leticia / Meng, Wenzhao / Adamski, Sharon / Baxter, Amy E. / Giles, Josephine R. / Weirick, Madison E. / McAllister, Christopher M. / Hicks, Amanda / Korte, Scott / Dougherty, Jeanette / Long, Sherea / D’Andrea, Kurt /

Hamilton, Jacob T. / Luning Prak, Eline T / Betts, Michael R. / Bates, Paul / Hensley, Scott E. / Greenplate, Allison R. / Wherry, E. John

medRxiv

Abstract	Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naive subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naive subjects remains poorly understood. In this study, we evaluated antibody responses and antigen-specific memory B cell responses over time in 33 SARS-CoV2 naive and 11 SARS-CoV2 recovered subjects. mRNA vaccination induced significant antibody and memory B cell responses against full-length SARS-CoV2 spike protein and the spike receptor binding domain (RBD). SARS-CoV2 naive individuals benefitted from both doses of mRNA vaccine with additional increases in antibodies and memory B cells following booster immunization. In contrast, SARS-CoV2 recovered individuals had a significant immune response after the first dose with no increase in circulating antibodies or antigen-specific memory B cells after the second dose. Moreover, the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses. The frequency of pre-vaccine antigen-specific memory B cells in SARS-CoV2 recovered individuals strongly correlated with post-vaccine antibody levels, supporting a key role for memory B cells in humoral recall responses to SARS-CoV2. This observation may have relevance for future booster vaccines and for responses to viral variants that partially escape pre-existing antibodies and require new humoral responses to be generated from memory B cells. Finally, post-boost antibody levels were not correlated with post-boost memory responses in SARS-CoV2 naive individuals, indicating that short-term antibody levels and memory B cells are complementary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.
Keywords	covid19
Language	English
Publishing date	2021-03-06
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.03.21252872
Database	COVID19

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Article ; Online: Rapid induction of antigen-specific CD4+ T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination

bioRxiv

Abstract: The SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses in healthy individuals following mRNA vaccination. ... ...

Abstract	The SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses in healthy individuals following mRNA vaccination. Vaccination induced rapid near-maximal antigen-specific CD4+ T cell responses in all subjects after the first vaccine dose. CD8+ T cell responses developed gradually after the first and second dose and were variable. Vaccine-induced T cells had central memory characteristics and included both Tfh and Th1 subsets, similar to natural infection. Th1 and Tfh responses following the first dose predicted post-boost CD8+ T cell and neutralizing antibody levels, respectively. Integrated analysis of 26 antigen-specific T cell and humoral responses revealed coordinated features of the immune response to vaccination. Lastly, whereas booster vaccination improved CD4+ and CD8+ T cell responses in SARS-CoV-2 naive subjects, the second vaccine dose had little effect on T cell responses in SARS-CoV-2 recovered individuals. Thus, longitudinal analysis revealed robust T cell responses to mRNA vaccination and highlighted early induction of antigen-specific CD4+ T cells.
Keywords	covid19
Language	English
Publishing date	2021-04-22
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.04.21.440862
Database	COVID19

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