In a recent study published on medRxiv* preprint server, Australian researchers report the durability and dynamics of protein-targeted antibody-mediated immunity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) recalled at least eight months after a breakthrough infection (BTI) with SARS-CoV-2 subvariants Omicron BA.1 and BA.2.
Study: Long-lasting reprogramming of neutralizing antibody responses following Omicron breakthrough infection. Image Credit: Nemes Laszlo / Shutterstock.com
Background
The continued emergence of highly transmissible and immuno-evasive Omicron subvariants, coupled with decreased immunity induced by the coronavirus disease 2019 (COVID-19) vaccine, has increased the frequency of BTIs in vaccinated against COVID-19. Previous studies of memory B cell-mediated responses and post-SARS-CoV-2 Delta or BA.1 BTI antibodies have shown rapid recall of the anti-S humoral response, S-targeted memory B cell reactivation and differentiation of antibody-secreting cells.
Additionally, Omicron BTIs among fully vaccinated individuals enhance the extent of neutralization, possibly due to novel antibodies targeting Omicron S epitopes or selective re-expansion of cross-protective memory B cells during vaccination.
Assessing the influence of BTIs with new Omicron subvariants on the extent and durability of humoral and memory B cell-mediated immunity could inform the development of vaccines optimized for maximum protection against B-cells. emerging infections with SARS-CoV-2.
About the study
In the present study, researchers are evaluating the initial kinetics of the recalled immune response after BTI BA.1 or BA.2 and profiled alterations in SARS-CoV-2 neutralization after recovery.
Twenty-six people vaccinated against COVID-19, consisting of three fully vaccinated people and 21 people who received a booster vaccination and two people who had previously been infected with the ancestral strain of SARS-CoV-2 who were subsequently vaccinated , were recruited as a result of BTI Omicron occurring after a median of 95 days of receiving the most recent vaccination.
Of the study participants, 19 of the 21 people had no history of SARS-CoV-2 infection and were vaccinated with protein S-encoding COVID-19 vaccines such as ChAdOx1 nCoV-19, BNT162b2 , NVX-CoV2373 and messenger RNA (mRNA)-1273.
BA.1 infections were confirmed by whole genome sequencing (WGS). In addition, participants’ nasal cavity and blood were collected for at least 247 days of follow-up.
SARS-CoV-2 ribonucleic acid (RNA) levels were determined using a quantitative polymerase chain reaction (qPCR) assay for the SARS-CoV-2 nucleocapsid (N) gene. 2. Anti-Omicron neutralization was modeled to estimate the durability of immune protection against symptomatic reinfections with SARS-CoV-2 variants of concern (COVs) with equivalent or greater immune evasion in people with hybrid immunity.
Linear mixed effects modeling was performed to estimate the average decay rate. BTIs were diagnosed using rapid antigen tests and PCR, while anti-N titers were determined using enzyme immunoassays (ELISA).
The ancestral SARS-CoV-2 strain was grown on Vero cells, while the BA.1, BA.2 and BA.4 subvariants were grown on Calu3 cells. SARS-CoV-2 infectivity was assessed using HAT-24 cells expressing human angiotensin-converting enzyme 2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2).
Percent viability and neutralization were determined based on relative fluorescent unit (RFU) values and mean ID50 values and CI50 values have been determined. Flow cytometry was performed to detect SARS-CoV-2 targeted B cells, with modeled antibody boosting and decay kinetics. Vaccine efficacy against different VOCs after BTI was estimated.
Results
All study participants developed symptomatic but mild BTI BA.1 or BA.2. These infections greatly enhanced their neutralization range against the causative VOCs, thereby expanding the neutralization range against the more evasive immune system BA.4.
Cross-reactive memory B cells against ancestral proteins and Omicron S were primarily developed by SARS-CoV-2 infection, with Omicron-targeted B cells or anti-SARS-CoV-2 antibodies recruited in a limited fashion Again.
Modeling estimates indicated that immune protection against symptomatic reinfections with closely related VOCs would have considerable durability, but would be undermined by novel and increasingly immune VOCs. Follow-up analyzes indicated long-lasting anti-Omicron neutralizing responses.
BTIs BA.1 and BA.2 showed comparable SARS-CoV-2 kinetics, with most infected individuals showing peak viral loads at enrollment and up to three days after symptom onset. SARS-CoV-2 replicated robustly during Omicron BTIs, despite previous vaccinations.
Serologic anti-N immunoglobulin G (IgG) titers were negligible at baseline time points; however, titers consistently increased from one week after BTI BA.1 and BA.2 symptom onset. Immune protection was estimated to be over 70% and lasted 705 days and 1607 days after BTI BA.1 and BA.2, respectively.
Viral load kinetics and seroconversion to N following breakthrough infection with Omicron BA.1 and BA.2. (A) Schematic of longitudinal sample collection after breakthrough infection of individuals vaccinated with Omicron BA.1 (n=10) or BA.2 (n=16). Each line represents a single subject and each dot represents a collection of samples (blue, nasal swab; red, blood; purple, nasal swab and blood). (B) Kinetics of SARS-CoV-2 viral load in nasal swabs measured by qPCR of the nucleocapsid (N) gene. (C) Kinetics of plasma IgG titers against SARS-CoV-2 (N) nucleocapsid after breakthrough infection with BA.1 (red) or BA.2 (blue). Subjects who have already been infected with SARS-CoV-2 are represented in closed circles. The thick lines represent the mean estimate of the piecewise linear regression model using the estimated parameters.
Even during peak neutralization of SARS-CoV-2, approximately one month after symptom onset, novel VOCs with three and ten times lower neutralization could reduce immune protection efficacy by 90.0% to 74 .0% and 47.0%, respectively. Among individuals with hybrid immunity against BTIs BA.1 and BA.2, the protective efficacy would decrease from 95.0% to 86.0% and 63.0%, respectively.
Recovery of BTIs from Omicron conferred markedly durable immune protection against antigenically similar strains; however, protection could be reversed rapidly by the emergence of more immune-evasive VOCs.
The breakthrough infection of Omicron BA.1 and BA.2 rapidly recalls neutralizing antibodies which are broad and long lasting. (A) Kinetics of plasma neutralizing activity following breakthrough infection against ancestral VIC01 or corresponding infecting Omicron BA.1 and BA.2 strains. The thick lines represent the mean estimate of the piecewise linear regression model using the estimated parameters. Plasma neutralization activity was measured using a live virus neutralization assay against clinical isolates of SARS-CoV-2 in HEK293T cells transduced with ACE2 and TMPRSS2. (B) Breakthrough plasma-mediated neutralization BA.1 and BA.2 against ancestral strains VIC01, Omicron BA.1, BA.2, and BA.4 at a median of 34 days after symptom onset. Data are presented as the median ± IQR. (C) Longitudinal decay kinetics of plasma neutralizing activity after breakthrough infection against ancestral VIC01 or matched infective Omicron BA.1 or BA.2 strains up to 4–7 months after symptom onset. The best-fitting decay slopes (thick lines) are shown. (D) IgG antibody titers against BA.1 peak for BA.1 pierced subjects (red) and against BA.2 peak for BA.2 pierced subjects (blue) after pre-incubation with BSA control (closed circles) or the ancestral Wuhan -hu-1 tip (open circles).
The team estimated that a protective efficacy of 70% for the SARS-CoV-2 homologous strain could be maintained for almost 4.5 and seven years for BTIs BA.1 and BA.2, respectively. Similarly, durable immune protection for the ancestral SARS-CoV-2 strain was estimated to persist for more than 8.5 years and 10 years for BTIs BA.1 and BA.2, respectively.
conclusion
Omicron’s BTIs have been found to induce long-lasting neutralizing immune responses by recalling cross-reactive and vaccine-induced memory B cells.
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WHAT
Toshniwal Paharia, Pooja Toshniwal Paharia. (2023, March 01). SARS-CoV-2 BA.1 and BA.2 breakthrough infections likely protect against BA.4 infection. News-Medical. Retrieved March 1, 2023, from https://www.news-medical.net/news/20230301/SARS-CoV-2-BA1-and-BA2-breakthrough-infections-likely-protect-against-BA4-infection.aspx.
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deputy
Toshniwal Paharia, Pooja Toshniwal Paharia. “SARS-CoV-2 BA.1 and BA.2 breakthrough infections likely protect against BA.4 infection”. News-Medical. March 1, 2023.
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Toshniwal Paharia, Pooja Toshniwal Paharia. “SARS-CoV-2 BA.1 and BA.2 breakthrough infections likely protect against BA.4 infection”. News-Medical. https://www.news-medical.net/news/20230301/SARS-CoV-2-BA1-and-BA2-breakthrough-infections-likely-protect-against-BA4-infection.aspx. (accessed March 01, 2023).
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Harvard
Toshniwal Paharia, Pooja Toshniwal Paharia. 2023. Breakthrough SARS-CoV-2 BA.1 and BA.2 infections likely protect against BA.4 infection. News-Medical, accessed March 1, 2023, https://www.news-medical.net/news/20230301/SARS-CoV-2-BA1-and-BA2-breakthrough-infections-likely-protect-against-BA4- .aspx infection.