Curated Papers > Recent research on high-impact "mRNA vaccines" (IF≥30, last 5 years)

mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.

Literature Information

DOI	10.1126/science.abm0829
PMID	34648302
Journal	Science (New York, N.Y.)
Impact Factor	45.8
JCR Quartile	Q1
Publication Year	2021
Times Cited	558
Keywords	mRNA vaccines, immune memory, SARS-CoV-2 variants
Literature Type	Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
ISSN	0036-8075
Pages	abm0829
Issue	374(6572)
Authors	Rishi R Goel, Mark M Painter, Sokratis A Apostolidis, Divij Mathew, Wenzhao Meng, Aaron M Rosenfeld, Kendall A Lundgreen, Arnold Reynaldi, David S Khoury, Ajinkya Pattekar, Sigrid Gouma, Leticia Kuri-Cervantes, Philip Hicks, Sarah Dysinger, Amanda Hicks, Harsh Sharma, Sarah Herring, Scott Korte, Amy E Baxter, Derek A Oldridge, Josephine R Giles, Madison E Weirick, Christopher M McAllister, Moses Awofolaju, Nicole Tanenbaum, Elizabeth M Drapeau, Jeanette Dougherty, Sherea Long, Kurt D'Andrea, Jacob T Hamilton, Maura McLaughlin, Justine C Williams, Sharon Adamski, Oliva Kuthuru, Ian Frank, Michael R Betts, Laura A Vella, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Scott E Hensley, Miles P Davenport, Paul Bates, Eline T Luning Prak, Allison R Greenplate, E John Wherry

TL;DR

This study investigates the durability of immune memory following mRNA vaccination against SARS-CoV-2, revealing that while antibody levels decline, they remain detectable for six months, and functional memory B cells increase over this period, effectively cross-binding multiple variants. The findings highlight the robust cellular immune memory elicited by mRNA vaccines, emphasizing their potential to sustain long-term immunity against SARS-CoV-2 and its variants.

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mRNA vaccines · immune memory · SARS-CoV-2 variants

Abstract

The durability of immune memory after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination remains unclear. In this study, we longitudinally profiled vaccine responses in SARS-CoV-2–naïve and –recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. By contrast, mRNA vaccines generated functional memory B cells that increased from 3 to 6 months postvaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity. Recall responses to vaccination in individuals with preexisting immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and its variants for at least 6 months after mRNA vaccination.

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Primary Questions Addressed

1. How do mRNA vaccines compare to other vaccine types in terms of inducing long-term immune memory against SARS-CoV-2?
2. What factors might influence the durability of immune memory generated by mRNA vaccines in different populations?
3. In what ways do the immune responses elicited by mRNA vaccines differ between SARS-CoV-2-naïve individuals and those who have recovered from COVID-19?
4. What implications do the findings on memory B cells and T cell responses have for booster vaccination strategies against emerging variants?
5. How might the observed cross-binding capabilities of memory B cells affect vaccine development for future coronavirus variants?

Key Findings

Research Background and Objectives

The study investigates the durability of immune memory following mRNA vaccination against SARS-CoV-2, focusing on antibody responses, memory B cells, and T cell responses over a six-month period. The research aims to provide insights into the immune response generated by mRNA vaccines and their effectiveness against variants of concern.

Main Methods/Materials/Experimental Design

The study involved 61 participants, divided into two groups: SARS-CoV-2 naïve (N=45) and SARS-CoV-2 recovered (N=16). Participants received either the Pfizer BNT162b2 or Moderna mRNA-1273 vaccines, with samples collected at six timepoints: pre-vaccination, post-first dose, post-second dose, and at 1, 3, and 6 months post-vaccination.

Key Experimental Steps

1. Sample Collection: Blood samples were collected to analyze antibody levels, memory B cells, and T cell responses.
2. Antibody Analysis: Enzyme-linked immunosorbent assays (ELISA) were used to measure anti-Spike and anti-RBD antibodies.
3. Memory B Cell Measurement: Flow cytometry was employed to quantify SARS-CoV-2-specific memory B cells.
4. T Cell Response Assessment: Activation-induced marker (AIM) assays were conducted to evaluate CD4+ and CD8+ T cell responses.

Key Results and Findings

1. Antibody Responses: Anti-Spike and anti-RBD IgG levels peaked one week after the second dose but declined over six months, with most individuals maintaining detectable levels.
2. Memory B Cells: The frequency of Spike-specific memory B cells increased from 3 to 6 months post-vaccination, particularly in SARS-CoV-2 naïve individuals. These cells demonstrated cross-reactivity with variants Alpha, Beta, and Delta.
3. T Cell Responses: CD4+ T cell responses were robust and stable at six months, while CD8+ T cell responses showed a decline. Early CD4+ T cell responses correlated with long-term antibody levels.

Main Conclusions/Significance/Innovation

The study concludes that mRNA vaccines induce durable immune memory characterized by robust antibody production, memory B cell formation, and stable CD4+ T cell responses for at least six months. The ability of memory B cells to cross-react with variants highlights the potential for mRNA vaccines to provide protection against emerging strains of SARS-CoV-2. The findings are significant for future vaccine strategies, including booster doses.

Research Limitations and Future Directions

1. Sample Size: The study's sample size, while substantial for immunological profiling, is still limited compared to larger epidemiological studies.
2. Kinetics of Responses: The timepoints may not fully capture the kinetics of immune responses; further longitudinal studies are needed.
3. Diversity of Participants: The cohort primarily consisted of young, healthy individuals, which may not represent responses in older or immunocompromised populations.

Future research should focus on:

• Evaluating the long-term durability of immune responses beyond six months.
• Assessing the impact of booster vaccinations on immune memory.
• Exploring the immune responses in diverse populations, including those with chronic health conditions.

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Literatures Citing This Work

1. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. - Aurélien Sokal;Giovanna Barba-Spaeth;Ignacio Fernández;Matteo Broketa;Imane Azzaoui;Andréa de La Selle;Alexis Vandenberghe;Slim Fourati;Anais Roeser;Annalisa Meola;Magali Bouvier-Alias;Etienne Crickx;Laetitia Languille;Marc Michel;Bertrand Godeau;Sébastien Gallien;Giovanna Melica;Yann Nguyen;Virginie Zarrouk;Florence Canoui-Poitrine;France Pirenne;Jérôme Mégret;Jean-Michel Pawlotsky;Simon Fillatreau;Pierre Bruhns;Felix A Rey;Jean-Claude Weill;Claude-Agnès Reynaud;Pascal Chappert;Matthieu Mahévas - Immunity (2021)
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3. Rapidly Declining SARS-CoV-2 Antibody Titers within 4 Months after BNT162b2 Vaccination. - Dong-Ho Jo;Dohsik Minn;Jaegyun Lim;Ki-Deok Lee;Yu-Min Kang;Kang-Won Choe;Kwang-Nam Kim - Vaccines (2021)
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... (548 more literatures)

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