Comprehensive antibody profiling of mRNA vaccination in children

Bartsch, Yannic C.; Denis, Kerri J St; Kapłonek, Paulina; Kang, Jaewon; Lam, Evan C.; Farkas, E; Davis, Jameson P.; Boribong, Brittany P.; Shreffler, Wayne G.; Balazs, Alejandro B.; Yonker, Lael M.; Alter, Galit

doi:10.1101/2021.10.07.463592

Cited by 14 publications

(16 citation statements)

References 53 publications

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“…Therefore, dose finding is crucial, particularly in vulnerable infants. For example, recent data on SARS-CoV2 mRNA vaccination with Comirnaty demonstrate that dose adjustments to 30 µg have resulted in poor immunogenicity in children under 5 years [138]. Most importantly, the potential future use of mRNA vaccines in vulnerable preterm infants must be above any safety concerns [136].…”

Section: Novel Vaccines: Mrna Technologymentioning

confidence: 99%

Immunization of preterm infants: current evidence and future strategies to individualized approaches

et al. 2022

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Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants benefit greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efficacy due to preterm infants’ distinct immunological features. A significant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specificities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specific recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained inflammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future.

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Section: Novel Vaccines: Mrna Technologymentioning

confidence: 99%

Immunization of preterm infants: current evidence and future strategies to individualized approaches

et al. 2022

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“…Encouragingly, the immune responses that have been generated display sufficient cross-coverage of the VOC, Omicron, with comparable immune responses to those reported in adults 8 . This could suggest that children develop a similar adaptive humoral immune response as seen in adults 9 , which may provide benefits to children as additional variants of concern emerge. While it is plausible that vaccine-induced anamnestic immunity may provide some level of protection in this population upon exposure, the durability of vaccine-induced immunity wanes in adolescents, and boosting may promote a robust barrier of immunity that will contribute to public health efforts to limit spread and prevent future hospitalizations and severe disease.…”

Section: Discussionmentioning

confidence: 98%

Durability and cross-reactivity of SARS-CoV-2 mRNA vaccine in adolescent children

Burns

Bartsch

Boribong

et al. 2022

Preprint

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Importance: Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals are causing increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for boosters in individuals ages 12 years or older calls for broader understanding of the adolescent immune profile after mRNA vaccination. Objective: We sought to test the durability and cross-reactivity of anti-SARS-CoV-2 serologic responses over a six-month time course in vaccinated adolescents against the wildtype and Omicron antigens. Design, Setting and Participants: Adolescents who received a full (two-dose) series of the Pfizer-BioNTech mRNA vaccination participated in this longitudinal cohort study from May 2021 to January 2022. Blood samples were collected in clinical settings from thirty-one adolescents, nineteen of whom provided samples at four timepoints (prior to vaccination, two to three weeks after first dose, two to four weeks after second dose and six months after complete series). Sera were analyzed for antibody responses against wildtype and Omicron variant SARS-CoV-2-specific proteins. Main Outcomes and Measures: The main outcome was to analyze vaccine-induced immune responses over time by ELISA, as well as their cross-reactivity between antibody responses against wildtype SARS-CoV-2 and the Omicron variant of concern. Results: Thirty-one adolescents provided a blood sample for at least one timepoint. The median age of the cohort was 13.9 years. Half of the cohort was male, and one quarter of the population was Hispanic. Anti-Spike and anti-RBD antibodies waned after six months, nearing pre-vaccination levels. After the second dose of the vaccine, adolescent children displayed equal sensitivity for the Omicron-RBD and wildtype SARS-CoV-2-RBD, as well as an upward trend of Omicron-reactive antibodies six months after vaccination. Waning mRNA vaccine-induced immunity in adolescents highlights a vulnerability in pediatric protection against SARS-CoV-2 infection. Conclusions and Relevance: Vaccine-induced immunity wanes in adolescents over time to near pre-vaccinated levels. Cross-reactivity of antibodies generated by adolescents display efficacy against Omicron. These findings highlight the need for SARS-CoV-2 boosters to protect adolescents from highly infectious variants, illness and post-COVID-19 complications.

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“…Cross-VOC antibody responses were observed at 50 and 100 μg vaccination, and humoral immunity to Omicron was observed at 100 μg vaccination. 171 Convalescent children who have been infected with SARS-CoV-2 and children vaccinated with two doses of BNT162b2 have reduced sensitivity to serum antibodies against the Omicron variants and have been more vulnerable to breakthrough infection. 131 A retrospective study conducted live virus and pseudovirus neutralization tests on the Omicron variant showed that the neutralizing effect of Omicron (B.1.1.529) variant decreased in serum from people who were vaccinated with BNT162b2 vaccine, mRNA-1273 vaccine, Sinopharm BBIBP-CorV vaccine, and the neutralizing activity against Omicron increased after booster vaccination.…”

Section: Omicron Variants Along With the Protective Effect Of Vaccinesmentioning

confidence: 99%

“…One study showed different responses in children (6–11 years old) vaccinated with varying doses of mRNA vaccines. Cross‐VOC antibody responses were observed at 50 and 100 μg vaccination, and humoral immunity to Omicron was observed at 100 μg vaccination 171 . Convalescent children who have been infected with SARS‐CoV‐2 and children vaccinated with two doses of BNT162b2 have reduced sensitivity to serum antibodies against the Omicron variants and have been more vulnerable to breakthrough infection 131 …”

Section: Prophylaxis and Treatment Of Omicron Variantmentioning

confidence: 99%

Sub‐lineages of the SARS‐CoV‐2 Omicron variants: Characteristics and prevention

Hong

Lou

et al. 2022

MedComm

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Since the start of the coronavirus disease 2019 (COVID‐19) pandemic, new variants of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) have emerged, accelerating the spread of the virus. Omicron was defined by the World Health Organization in November 2021 as the fifth “variant of concern” after Alpha, Beta, Gamma, and Delta. In recent months, Omicron has become the main epidemic strain. Studies have shown that Omicron carries more mutations than Alpha, Beta, Gamma, Delta, and wild‐type, facilitating immune escape and accelerating its transmission. This review focuses on the Omicron variant's origin, transmission, main biological features, subvariants, mutations, immune escape, vaccination, and detection methods. We also discuss the appropriate preventive and therapeutic measures that should be taken to address the new challenges posed by the Omicron variant. This review is valuable to guide the surveillance, prevention, and development of vaccines and other therapies for Omicron variants. It is desirable to develop a more efficient vaccine against the Omicron variant and take more effective measures to constrain the spread of the epidemic and promote public health.

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Comprehensive antibody profiling of mRNA vaccination in children

Cited by 14 publications

References 53 publications

Immunization of preterm infants: current evidence and future strategies to individualized approaches

Immunization of preterm infants: current evidence and future strategies to individualized approaches

Durability and cross-reactivity of SARS-CoV-2 mRNA vaccine in adolescent children

Sub‐lineages of the SARS‐CoV‐2 Omicron variants: Characteristics and prevention

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