Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

Tang, Juanjie; Novak, Tanya; Hecker, Julian; Grubbs, Gabrielle; Zahra, Fatema Tuz; Bellusci, Lorenza; Pourhashemi, Sara; Chou, Janet; Moffitt, Kristin; Halasa, Natasha; Schwartz, Stephanie P; Walker, Tracie C; Tarquinio, Keiko M.; Zinter, Matt S.; Staat, Mary Allen; Gertz, Shira J.; Cvijanovich, Natalie Z.; Schuster, Jennifer E; Loftis, Laura; Coates, Bria M.; Mack, Elizabeth H.; Irby, Katherine; Fitzgerald, Julie C; Rowan, Courtney M.; Kong, Michele; Flori, Heidi R.; Maddux, Aline B; Shein, Steven L.; Crandall, Hillary; Hume, Janet R.; Hobbs, Charlotte V.; Tremoulet, Adriana H.; Shimizu, Chisato; Burns, Jane C.; Chen, Sabrina R.; Moon, Hye Kyung; Lange, Christoph; Randolph, Adrienne G.; Khurana, Surender

doi:10.1038/s41467-022-30649-1

Cited by 46 publications

(55 citation statements)

References 35 publications

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“…Neutralizing antibody responses were consistently higher with mRNA-1273.214, compared to mRNA-1273, in participants with and without evidence of prior SARS-CoV-2 infection. Given the epidemiological data suggestive of decreasing vaccine effectiveness against infection with omicron and that break-through infections can occur in vaccinated individuals, including those with prior SARS-CoV-2 infection, [8][9][10]17,28 it is important to be able to boost immune responses in this group. The mechanisms of an increased antibody response with vaccines that contain both the ancestral SARS-CoV-2-spike protein sequence as well as that of an antigenically-divergent variant could include the generation of new memory immune responses but are yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6][7] Omicron and omicron subvariants continue to cause significant morbidity and mortality and re-infection with omicron or a subvariant is possible, especially in unvaccinated individuals. [8][9][10] Immunization with an mRNA-1273 50-µg booster dose increases neutralizing antibody responses against variants and booster doses enhance vaccine effectiveness against Covid-19. [11][12][13][14][15][16] Nonetheless, effectiveness of the currently authorized vaccines against omicron is decreased compared to other variants [17][18][19][20] and consequently, a second booster dose was authorized in the US for immunocompromised individuals and adults >50 years of age in the midst of omicron waves.…”

Section: Introductionmentioning

confidence: 99%

“…3-7 Omicron and omicron subvariants continue to cause significant morbidity and mortality and re-infection with omicron or a subvariant is possible, especially in unvaccinated individuals. 8-10…”

Section: Introductionmentioning

confidence: 99%

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A Bivalent Omicron-containing Booster Vaccine Against Covid-19

Chalkias

Harper

Vrbicky

et al. 2022

Preprint

116

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Background Updated vaccination strategies against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern are needed. Interim results of the safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster candidate are presented. Methods In this ongoing, phase 2/3 trial, the 50-μg bivalent vaccine mRNA-1273.214 (25-μg each ancestral Wuhan-Hu-1 and omicron B.1.1.529 spike SARS-CoV-2 mRNAs) was compared to the authorized 50-μg mRNA-1273 booster in adults who previously received 2-dose primary series of 100-μg mRNA-1273 and a first booster dose of 50-μg mRNA-1273 at least 3 months prior. Primary objectives were safety and reactogenicity, and immunogenicity of 50-μg mRNA-1273.214 compared with 50-μg mRNA-1273. Immunogenicity data 28 days after the booster dose are presented. Results Four hundred thirty-seven and 377 participants received 50-μg of mRNA-1273.214, or mRNA-1273, respectively. Median time between first and second booster doses of mRNA-1273.214 and mRNA-1273 were similar (136 and 134 days, respectively). In participants with no prior SARS-CoV-2 infection, observed omicron neutralizing antibody geometric mean titers (GMTs [95% confidence interval]) after the mRNA-1273.214 and mRNA-1273 booster doses, were 2372.4 (2070.6−2718.2) and 1473.5 (1270.8−1708.4) respectively and the model-based GMT ratio (97.5% confidence interval) was 1.75 (1.49−2.04). All pre-specified non-inferiority (ancestral SARS-CoV-2 with D614G mutation [D614G] GMT ratio; ancestral SARS-CoV-2 [D614G] and omicron seroresponse rates difference) and superiority primary objectives (omicron GMT ratio) for mRNA-1273.214 compared to mRNA-1273 were met. Additionally, mRNA-1273.214 50-μg induced a potent neutralizing antibody response against omicron subvariants BA.4/BA.5 and higher binding antibody responses against alpha, beta, gamma, delta and omicron variants. Safety and reactogenicity profiles were similar and well-tolerated for both vaccines groups. Conclusion The bivalent vaccine mRNA-1273.214 50-μg was well-tolerated and elicited a superior neutralizing antibody response against omicron, compared to mRNA-1273 50-μg, and a non-inferior neutralizing antibody response against the ancestral SARS-CoV-2 (D614G), 28 days after immunization, creating a new tool as we respond to emerging SARS-CoV-2 variants.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Bivalent Omicron-containing Booster Vaccine Against Covid-19

Chalkias

Harper

Vrbicky

et al. 2022

Preprint

116

View full text Add to dashboard Cite

show abstract

“…In comparison with adults, children appear to have a more potent first immune response to COVID-19 and can eliminate the infection quickly. 137 However, since antibodies are expected to play a role in preventing re-infection, the findings raise concerns about how effectively protected infants are against subsequent diseases.…”

Section: Re-infection With Omicronmentioning

confidence: 99%

“…Based on research, although children have the same symptoms and quantities of virus in their systems, their involvement with SARS‐CoV‐2 is more likely to induce antibodies against the virus than adults. In comparison with adults, children appear to have a more potent first immune response to COVID‐19 and can eliminate the infection quickly 137 . However, since antibodies are expected to play a role in preventing re‐infection, the findings raise concerns about how effectively protected infants are against subsequent diseases.…”

Section: Introductionmentioning

confidence: 99%

OMICRON: Virology, immunopathogenesis, and laboratory diagnosis

Bazargan

Elahi

Esmaeilzadeh

2022

The Journal of Gene Medicine

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Since its emersion, coronavirus disease 2019 (COVID‐19) has been a significant global dilemma. Several mutations in the severe acute respiratory virus (SARS‐Co‐2) genome has given rise to different variants with various levels of transmissibility, severity and mortality. Up until November 2021, the variants of concern declared by the World Health Organization were Alpha, Beta, Delta and Gamma. Since then, a novel variant named Omicron (B.1.1.529) has been developed. BA.1, BA.1.1, BA.2 and BA.3 are four known subvariants of Omicron. The Omicron variant involves new mutations in its spike protein, most of which are in its receptor binding site, and increase its transmissibility and decrease its antibody and vaccine response. Understanding the virology and mutations of Omicron is necessary for developing diagnostic and therapeutic methods. Moreover, important issues, such as the risk of re‐infection, the response to different kinds of vaccines, the need for a booster vaccine dose and the increased risk of Omicron infection in pediatrics, need to be addressed. In this article, we provide an overview of the biological and immunopathological properties of Omicron and its subvariants, its clinical signs and symptoms, Omicron and pediatrics, vaccines against Omicron, re‐infection with Omicron, diagnostic approaches and specific challenges of Omicron in the successful control and management of the rapid global spread of this variant.

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How Do We Stop the Spread of SARS-CoV-2 in Young Children?

Kim

Englund

2022

JAMA Netw Open

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Early in the COVID-19 pandemic, SARS-CoV-2 infection in children was considered to be uncommon and to not cause serious disease. We now know that children can be infected and spread SARS-CoV-2 and that the rates and severity of SARS-CoV-2 infection differ among children of various ages, children with different underlying conditions, and children with different viral variants. During the Omicron variant surge, children aged 0 to 4 years had the highest rates of hospitalization compared with older children (15.2 hospitalizations per 100 000 people among children aged 0-4 years vs 2.6 hospitalizations per 100 000 people among children aged 5-11 years and 5.8 hospitalizations per 100 000 people among children aged 12-18 years during its peak in January 2022). 1 SARS-CoV-2 has

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Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

Cited by 46 publications

References 35 publications

A Bivalent Omicron-containing Booster Vaccine Against Covid-19

A Bivalent Omicron-containing Booster Vaccine Against Covid-19

OMICRON: Virology, immunopathogenesis, and laboratory diagnosis

How Do We Stop the Spread of SARS-CoV-2 in Young Children?

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