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Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant.

ABSTRACT: Omicron variant (B.1.1.529) infections are rapidly expanding worldwide, often in settings where the Delta variant (B.1.617.2) was dominant. We investigated whether neutralizing immunity elicited by Omicron infection would also neutralize the Delta variant and the role of prior vaccination. We enrolled 23 South African participants infected with Omicron a median of 5 days post-symptoms onset (study baseline) with a last follow-up sample taken a median of 23 days post-symptoms onset. Ten participants were breakthrough cases vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV2.S. In vaccinated participants, neutralization of Omicron increased from a geometric mean titer (GMT) FRNT₅₀ of 28 to 378 (13.7-fold). Unvaccinated participants had similar Omicron neutralization at baseline but increased from 26 to only 113 (4.4-fold) at follow-up. Delta virus neutralization increased from 129 to 790, (6.1-fold) in vaccinated but only 18 to 46 (2.5-fold, not statistically significant) in unvaccinated participants. Therefore, in Omicron infected vaccinated individuals, Delta neutralization was 2.1-fold higher at follow-up relative to Omicron. In a separate group previously infected with Delta, neutralization of Delta was 22.5-fold higher than Omicron. Based on relative neutralization levels, Omicron re-infection would be expected to be more likely than Delta in Delta infected individuals, and in Omicron infected individuals who are vaccinated. This may give Omicron an advantage over Delta which may lead to decreasing Delta infections in regions with high infection frequencies and high vaccine coverage.

SUBMITTER: Khan K

PROVIDER: S-EPMC8722619 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant.

Khan Khadija K Karim Farina F Cele Sandile S San James Emmanuel JE Lustig Gila G Tegally Houriiyah H Rosenberg Yuval Y Bernstein Mallory M Ganga Yashica Y Jule Zesuliwe Z Reedoy Kajal K Ngcobo Nokuthula N Mazibuko Matilda M Mthabela Ntombifuthi N Mhlane Zoey Z Mbatha Nikiwe N Miya Yoliswa Y Giandhari Jennifer J Ramphal Yajna Y Naidoo Taryn T Manickchund Nithendra N Magula Nombulelo N Abdool Karim Salim S SS Gray Glenda G Hanekom Willem W von Gottberg Anne A Milo Ron R Gosnell Bernadett I BI Lessells Richard J RJ Moore Penny L PL de Oliveira Tulio T Moosa Mahomed-Yunus S MS Sigal Alex A

medRxiv : the preprint server for health sciences 20220128

Omicron variant (B.1.1.529) infections are rapidly expanding worldwide, often in settings where the Delta variant (B.1.617.2) was dominant. We investigated whether neutralizing immunity elicited by Omicron infection would also neutralize the Delta variant and the role of prior vaccination. We enrolled 23 South African participants infected with Omicron a median of 5 days post-symptoms onset (study baseline) with a last follow-up sample taken a median of 23 days post-symptoms onset. Ten participa ...[more]

PMID: 34981076

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Project description:The neutralizing antibody response is a key component of adaptive immunity and a primary protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The increased transmissibility of the SARS-CoV-2 Delta variant and its capacity to cause more severe disease could be linked to a significant reduction in neutralizing antibodies generated during a previous infection or vaccination. We analyzed blood samples from 162 unvaccinated health care workers (HCWs) collected 1 to 3 months postinfection and from 263 vaccinated health care workers 1 month after the last injection. We have compared the neutralizing antibody titers obtained using two virus strains, B.1.160 and B.1.617.2 (Delta variant). Binding antibody concentrations were measured by an immunoassay. The median neutralizing antibody titer against the B.1.160 strain was 128 (interquartile range [IQR], 16 to 256) and 32 (IQR, 8 to 128) against the Delta variant. To obtain a neutralizing antibody titer of 32 or 64, a binding antibody concentration of 182 binding antibody units (BAU)/mL (IQR, 81 to 974) was required with the strain B.1.160, while a concentration of 2,595 BAU/mL (IQR, 1,176 to 5,353) was required with the Delta variant. Our data indicate that antibodies neutralize the SARS-CoV-2 Delta variant 4 times less efficiently than they neutralize an earlier strain. Half of the HCWs had decreased protection from 94% to 76.8% or less for the same total antibody concentration. But neutralization might be correlated with other immune responses. The contributions of other responses, such as those of the T cell and B cell systems, to protection require further investigation. IMPORTANCE Recent studies showed that the neutralizing antibody titer is an important contributor to protection against SARS-CoV-2. With the emergence of new variants, the question arises of maintaining the neutralizing capacities of vaccines and/or of a past infection. We had protective data associated with total antibody concentrations and neutralizing antibody titers for a B.1.160 strain. We showed that to maintain the same levels of protection and, therefore, the same levels of neutralizing antibodies, a total antibody concentration 8.5 times greater is required with the Delta strain. (This study has been registered at ClinicalTrials.gov under registration no. NCT04385108.).

Project description:ImportanceStudies have reported increased risk of autoimmune sequelae after SARS-CoV-2 infection. However, risk may potentially be attenuated by milder Omicron (B.1.1.529) variant infection and availability of booster vaccination.ObjectiveTo estimate the 300-day risk of new-incident autoimmune sequelae after SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection in adults who received COVID-19 vaccines and boosters, compared with a contemporary control group without infection.Design, setting, and participantsThis cohort study in Singapore enrolled adults from September 1, 2021, to March 7, 2022, and followed up for 300 days. Participants were adults aged 18 years or older with SARS-CoV-2 infection during the predominance of the Delta and Omicron BA.1 or BA.2 variants and were still alive at 30 days after COVID-19 diagnosis.ExposureThe national SARS-CoV-2 testing registry was used to construct cohorts of adults with SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection (hereafter, cases) and a contemporaneous group with negative polymerase chain reaction or rapid antigen test results (hereafter, controls).Main outcomes and measuresNew-incident autoimmune diagnoses after SARS-CoV-2 infection. This information was recorded in the MediClaims national health care claims database and identified 31 to 300 days after index date of infection. Risks and excess burdens were estimated using Cox proportional hazards regression model with overlap weights applied.ResultsIn total, 1 766 036 adults (915 096 females [51.9%]; mean [SD] age, 49 [18] years) were included in the study population, with 480 082 (27.2%) categorized as cases and 1 285 954 (72.8%) as controls. Of these adults, 73.1% had Chinese, 13.7% Malay, and 9.9% Indian ethnicity. There were 104 179 cases and 666 575 controls included during the Delta variant-predominance transmission, while 375 903 cases and 619 379 controls were included during the Omicron variant-predominance transmission. During the Delta variant period, 81.1% of cases had completed primary vaccination; during the Omicron variant period, 74.6% of cases received boosters. No significantly elevated risk of 12 prespecified autoimmune sequelae was recorded across the Omicron and Delta variant cohorts. Elevated risks of inflammatory bowel disease (adjusted hazard ratio [AHR], 2.23; 95% CI, 1.45-3.46; P < .001) and bullous skin disorders (AHR, 4.88; 95% CI, 2.47-9.66; P < .001) were observed only in the subset of COVID-19 cases requiring hospitalization during the predominance of the Omicron variant. While elevated risk of vasculitis (AHR, 5.74; 95% CI, 1.48-22.23; P = .01) was observed in vaccine-breakthrough Omicron variant infections, no increased risk of vasculitis was observed in the corresponding subgroup who received boosters.Conclusions and relevanceThis cohort study observed no significantly elevated long-term risk of autoimmune sequelae after SARS-CoV-2 Delta and Omicron BA.1 or BA.2 variant infection, except for a modestly increased risk of inflammatory bowel disease and bullous skin disorders in the hospitalized subgroup during the predominance of the Omicron variant. Booster vaccination appeared to mitigate the risk of long-term autoimmune sequelae.

Project description:BackgroundThe SARS-CoV-2 Delta variant was first identified in the U.S. in March 2021 and has rapidly become the predominant lineage across the U.S. due to increased transmissibility, immune evasion and vaccine breakthrough. The aim of this study was to better understand the genetic diversity and the potential impact of mutations observed in SARS-CoV-2 viruses circulating in the U.S. in vaccinated individuals.ResultsWhole genome sequencing was performed on thirty-four SARS-CoV-2 positive samples using the Oxford Nanopore MinION. Evolutionary genomic analysis revealed two novel mutations, ORF1b:V2354F and a premature stop codon, ORF7a:Q94*, identified in a cluster of SARS-CoV-2 Delta isolates collected from vaccinated individuals in Colorado. The ORF1b:V2354F mutation, corresponding to NSP15:V303F, may induce a conformational change and result in a disruption to a flanking beta-sheet structure. The premature stop codon, ORF7a:Q94*, truncates the transmembrane protein and cytosolic tail used to mediate protein transport. This may affect protein localization to the ER-Golgi. In addition to these novel mutations, the cluster of vaccinated isolates contain an additional mutation in the spike protein, at position 112, compared to the Delta variant defining mutations. This mutation, S112L, exists in isolates previously obtained in the U.S. The S112L mutation substitutes a bulky hydrophobic side chain for a polar side chain, which results in a non-conservative substitution within the protein that may affect antibody-binding affinity. Additionally, the vaccinated cluster of isolates contains non-synonymous mutations within ORF8 and NSPs which further distinguish this cluster from the respective ancestral Delta variant.ConclusionsThese results show there is an emerging sub-lineage of the ancestral Delta variant circulating in the U.S. As mutations emerge in constellations, those with a potentially beneficial advantage to the virus may continue to circulate while others will cease.

Project description:Despite the success of COVID-19 vaccines in preventing infection and/or severe disease, there has been an increase in SARS-CoV-2 infections in vaccinated individuals owing to the waning vaccine-derived immunity, and the emergence of new variants which encode escape mutations in Spike. Following breakthrough infection in vaccinated individuals, an increase in neutralization breadth has been observed in sera/plasma. However, how exposure to a heterologous Spike broadens the neutralizing response at the monoclonal antibody (mAb) level is not fully understood. Through isolation of 119 mAbs from three individuals receiving two doses of BNT162b2 vaccine before becoming Delta or Omicron/BA.1 infected, we show that serum breadth occurs due to the presence of somatically mutated mAbs with broad neutralization activity indicative of re-activation and maturation of B cells generated through previous COVID-19 vaccination. Isolated mAbs frequently show reduced neutralization of current circulating variants including BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 confirming continuous selective pressure on Spike to evolve and evade neutralization. However, isolation of mAbs that display effective cross-neutralization against all variants indicates the presence of conserved epitopes on the receptor binding domain and a lesser extent the N-terminal domain. These findings have implications for the selection of Spike antigens for next-generation COVID-19 vaccines. IMPORTANCE With the emergence of SARS-CoV-2 viral variants, there has been an increase in infections in vaccinated individuals. Here, we isolated monoclonal antibodies (mAbs) from individuals experiencing a breakthrough infection (Delta or BA.1) to determine how exposure to a heterologous Spike broadens the neutralizing antibody response at the monoclonal level. All mAbs isolated had reactivity to the Spike of the vaccine and infection variant. While many mAbs showed reduced neutralization of current circulating variants, we identified mAbs with broad and potent neutralization of BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 indicating the presence of conserved epitopes on Spike. These results indicate that variant-based vaccine boosters have the potential to broaden the vaccine response.

Dataset Information

Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant.

Publications

Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant.

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