Delayed-interval BNT162b2 mRNA COVID-19 vaccination enhances humoral immunity and induces robust T cell responses

Hall, Victoria; Ferreira, Victor H; Wood, Heidi; Ierullo, Matthew; Majchrzak-Kita, Beata; Manguiat, Kathy; Robinson, Alyssia; Kulasingam, Vathany; Humar, Atul; Kumar, Deepali

doi:10.1038/s41590-021-01126-6

Cited by 99 publications

(88 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Humans receive a 2-dose standard regimen of mRNA-LNP vaccines at 3 to 4 weeks intervals (Walsh et al, 2020) and booster shots at different time points. Our data are strongly supported by recent studies showing that a delay of the second dose of an mRNA vaccine from 3 weeks to 3 months significantly improves the antibody response (Hall et al, 2022; Ooi and B, 2022; Parry et al, 2022). Indeed, inflammation has been related to a poor responsiveness to vaccination in earlier studies (Trzonkowski et al, 2003), and it is rational to hypothesize that the acute inflammatory side effects of the LNP platform negatively impedes induction of antibody responses during the second dose administration.…”

Section: Discussionsupporting

confidence: 89%

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Qin

Igyártó

2022

Preprint

View full text Add to dashboard Cite

Billions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. Here we bring experimental evidence that pre-exposure to mRNA-LNPs or its LNP component has effects on both innate and adaptive immune responses. Pre-exposure to mRNA-LNPs led to long-term, platform-specific inhibition of the adaptive immune responses. As such, mice responded with lower antibody responses when exposed the second time to the mRNA-LNP platform, but with undisturbed adaptive immune responses to protein-based Alum or AddaVax-adjuvanted vaccines. On the other hand, we report that after pre-exposure to mRNA-LNPs, resistance of mice to heterologous infections with influenza virus and Candida albicans is likely enhanced. Interestingly, mice pre-exposed to mRNA-LNPs can pass down the acquired immune traits to their offspring, providing better protection. In summary, the mRNA-LNP vaccine platform induces long-term immunological changes that can affect both humoral responses and heterologous protection against infections. More studies are needed to understand in-depth the mechanisms responsible for these effects.

show abstract

Section: Discussionsupporting

confidence: 89%

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Qin

Igyártó

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…It has recently been reported that a stronger humoral response is induced at extended intervals compared to the standard 3-4 week interval in the homologous BNT162b2 vaccination. 11 , 12 , 13 Extended intervals of booster dose may result in higher neutralizing activity and wider breadth of humoral responses through germinal center responses including somatic hypermutation and affinity maturation. 14 Comparison of immune responses in the heterologous vaccination to homologous BNT162b2 vaccination at similarly extended intervals may allow assessment of this issue.…”

Section: Discussionmentioning

confidence: 99%

Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity

Bae

Choi

et al. 2022

Clinical Microbiology and Infection

View full text Add to dashboard Cite

“…In line with our observation, vaccine efficacy has been shown to increase with the interval between the 1 st and 2 nd vaccine dose (Voysey et al, 2021). Prolonged affinity maturation yielding higher affinity B cells for plasma cell maturation upon the administration of the 2nd vaccine dose may be of importance in this process (Hall et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens

Wang

Muecksch

Münn

et al. 2022

Preprint

View full text Add to dashboard Cite

The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID- 19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV2.S and two-dose ChAdOx1 or combination ChAdOx1/mRNA vaccination. Plasma neutralizing activity as well as the magnitude, clonal composition and antibody maturation of the RBD-specific memory B cell compartment showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS-CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV2.S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.

show abstract

Delayed-interval BNT162b2 mRNA COVID-19 vaccination enhances humoral immunity and induces robust T cell responses

Cited by 99 publications

References 12 publications

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion

Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity

Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens

Contact Info

Product

Resources

About