SARS-CoV-2–specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge

Woldemeskel, Bezawit A.; Garliss, Caroline C.; Aytenfisu, Tihitina Y; Johnston, Trevor S; Beck, Elizabeth; Dykema, Arbor G.; Frumento, Nicole; Wright, Desiree A; Yang, Andrew H; Damanakis, Alexander; Laeyendecker, Oliver; Cox, Andrea L.; Mostafa, Heba H.; Karaba, Andrew H; Blankson, Joel N.

doi:10.1172/jci.insight.159474

Cited by 19 publications

(19 citation statements)

References 34 publications

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“…Breakthrough Omicron infections are documented in individuals with a range of vaccine-induced protective antibody titers ( 29 ). Booster vaccination can increase antibody levels and activity but cannot absolutely prevent breakthrough infection ( 30 ). Overall, it has been observed that Omicron is the most neutralization resistant SARS-CoV-2 variant of concern (VOC) ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Prior Vaccination Exceeds Prior Infection in Eliciting Innate and Humoral Immune Responses in Omicron Infected Outpatients

Lee

Walter

Knabl³

et al. 2022

Front. Immunol.

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Antibody response following Omicron infection is reported to be less robust than that to other variants. Here we investigated how prior vaccination and/or prior infection modulates that response. Disease severity, antibody responses and immune transcriptomes were characterized in four groups of Omicron-infected outpatients (n=83): unvaccinated/no prior infection, vaccinated/no prior infection, unvaccinated/prior infection and vaccinated/prior infection. The percentage of patients with asymptomatic or mild disease was highest in the vaccinated/no prior infection group (87%) and lowest in the unvaccinated/no prior infection group (47%). Significant anti-Omicron spike antibody levels and neutralizing activity were detected in the vaccinated group immediately after infection but were not present in the unvaccinated/no prior infection group. Within two weeks, antibody levels against Omicron, increased. Omicron neutralizing activity in the vaccinated group exceeded that of the prior infection group. No increase in neutralizing activity in the unvaccinated/no prior infection group was seen. The unvaccinated/prior infection group showed an intermediate response. We then investigated the early transcriptomic response following Omicron infection in these outpatient populations and compared it to that found in unvaccinated hospitalized patients with Alpha infection. Omicron infected patients showed a gradient of transcriptional response dependent upon whether or not they were previously vaccinated or infected. Vaccinated patients showed a significantly blunted interferon response as compared to both unvaccinated Omicron infected outpatients and unvaccinated Alpha infected hospitalized patients typified by the response of specific gene classes such as OAS and IFIT that control anti-viral responses and IFI27, a predictor of disease outcome.

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Section: Discussionmentioning

confidence: 99%

Prior Vaccination Exceeds Prior Infection in Eliciting Innate and Humoral Immune Responses in Omicron Infected Outpatients

Lee

Walter

Knabl³

et al. 2022

Front. Immunol.

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“…These T cells responses were maintained at least for 6 months after booster dose [103]. Also, mRNA booster vaccine recipients had significantly stronger T cells responses to Omicron S-protein at the time of breakthrough infection [104]. In another study, it was found that about 15% vaccinated individuals (5 out of 32) exhibited a loss of CD8 T cell recognition of Omicron [105].…”

Section: Vaccine-induced T Cell Immune Responses Against Omicron Variantmentioning

confidence: 95%

Humoral and Cellular Immune Responses of COVID-19 vaccines against SARS-Cov-2 Omicron variant: a systemic review

Chen¹,

Zhang²,

Wang³

et al. 2022

Int. J. Biol. Sci.

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has undergone multiple mutations since its emergence, and its latest variant, Omicron (B.1.1.529), is the most contagious variant of concern (VOC) which poses a major and imminent threat to public health. Since firstly reported by World Health Organization (WHO) in November 2021, Omicron variant has been spreading rapidly and has become the dominant variant in many countries worldwide. Omicron is the most mutated variant so far, containing 60 mutations in its genome, including 37 mutations in the S-protein. Since all current COVID-19 vaccines in use were developed based on ancestral SARS-CoV-2 strains, whether they are protective against Omicron is a critical question which has been the center of study currently. In this article, we systemically reviewed the studies regarding the effectiveness of 2-or 3-dose vaccines delivered in either homologous or heterologous manner. The humoral and cellular immune responses elicited by various vaccine regimens to protect against Omicron variant are discussed. Current understanding of the molecular basis underlying immune escape of Omicron was also analyzed. These studies indicate that two doses of vaccination are insufficient to elicit neutralizing antibody responses against Omicron variant. Nevertheless, Omicron-specific humoral immune responses can be enhanced by booster dose of almost all type vaccines in certain degree, and heterologous vaccination strategy may represent a better choice than homogenous regimens. Intriguingly, results of studies indicate that all current vaccines are still able to elicit robust T cell response against Omicron. Future focus should be the development of Omicron variant vaccine, which may induce potent humoral as well as cellular immune responses simultaneously against all known variants of the SARS-CoV-2 virus.

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“…In this regard, however, the observations reported by Servellita and coworkers should be mentioned that showed Omicron breakthrough infections appear to be less immunogenic than those produced by Delta [ 12 ]. Interestingly, breakthrough infections by Omicron in boosted vaccinated individuals have also been shown to result in a marked increase in the serum neutralizing activity against Omicron as well as the VOCs Alpha, Beta, and Delta, as reported by Woldemeskel and coworkers [ 13 ].…”

Section: Discussionmentioning

confidence: 68%

Omicron Breakthrough Infection After Heterologous Prime-Boost Vaccination Induces a Vigorous Antibody Response

Varese

Mazzitelli

Díaz

et al. 2022

The Journal of Infectious Diseases

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SARS-CoV-2–specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge

Cited by 19 publications

References 34 publications

Prior Vaccination Exceeds Prior Infection in Eliciting Innate and Humoral Immune Responses in Omicron Infected Outpatients

Prior Vaccination Exceeds Prior Infection in Eliciting Innate and Humoral Immune Responses in Omicron Infected Outpatients

Humoral and Cellular Immune Responses of COVID-19 vaccines against SARS-Cov-2 Omicron variant: a systemic review

Omicron Breakthrough Infection After Heterologous Prime-Boost Vaccination Induces a Vigorous Antibody Response

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