SARS-CoV-2 variants BA.4 and BA.5 show substantial immune escape compared with BA.1 and BA.2 (2022)

SARS-CoV-2 variants BA.4 and BA.5 show substantial immune escape compared with BA.1 and BA.2 (1)By Neha MathurMay 26 2022Reviewed by Emily Henderson, B.Sc.

In a recent study posted to the bioRxiv* pre-print server, researchers characterized the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) Omicron’s new sub-lineages, BA.4, BA.5, and BA.3. They reported the antigenic characterization of these sublineages compared to the previously identified Omicron sublineages, BA.1 and BA.2.

SARS-CoV-2 variants BA.4 and BA.5 show substantial immune escape compared with BA.1 and BA.2 (2)Study: Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum. ​​​​​​​Image Credit: NIAID

(Video) BA.5 causes more severe disease

Background

Omicron sublineages, BA.4 and BA.5, were reported from Gauteng in South Africa in April 2022. It's possible that they are fueling a new wave of infections in South Africa, which could eventually erupt worldwide. Both BA.4/5 appear to have evolved from BA.2 and have similar SARS-CoV-2 spike (S) glycoprotein sequences. Additionally, they contain mutations in the S receptor-binding domain (RBD), viz., the R493Q mutation (also found in the SARS-CoV-2 Wuhan-Hu 1 strain), as well as L452R and F486V substitutions.

The substitutions in the BA.4/5 RBDs, L452R, and F486V are of most concern because of their potential to confer immune invasion. Both the mutations are close to the angiotensin-converting enzyme 2 (ACE2) receptor surface, hence can modulate RBD-ACE2 affinity and the neutralizing capacity of natural or vaccine acquired immunity. While the reversion mutation Q493, which also lies within the ACE2, likely reduces the escape from responses to earlier SARS-CoV-2 strains.

About the study

In the present study, researchers reported antigenic characteristics of the Omicron sub-lineages BA.4 and BA.5 (BA.4/5). To this end, the team constructed pseudotyped lentiviruses (pLVs) expressing the S gene of the Omicron sub-lineages BA.1, BA.1.1, BA.2, BA.3, and BA.4/5. They used Wuhan-Hu 1 related strain, Victoria, as the control.

SARS-CoV-2 variants BA.4 and BA.5 show substantial immune escape compared with BA.1 and BA.2 (3)

The Omicron sub-lineage compared to BA.4/5. (A) Comparison of S protein mutations of Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4/5 with NTD and RBD boundaries indicated. (B) Position of RBD mutations (grey surface with the ACE2 footprint in dark green). Mutations common to all Omicron lineages are shown in white (Q493R which is reverted in BA.4/5 is shown with a cross), those common to BA.1 and BA.1.1 in cyan, those unique to BA.1.1 in blue and those unique to BA.2 in magenta. Residue 371 (yellow) is mutated in all Omicron viruses but differs between BA.1 and BA.2. The N343 glycan is shown as sticks with a transparent surface.

(Video) Omicron BA.5 is Overtaking The US: Immune Boosting Strategies

Next, the team collected serum samples of coronavirus disease 2019 (COVID-19) vaccinated individuals to perform neutralization assays. Specifically, they obtained 41 and 20 serum samples 28 days following the third dose of the AZD1222 and BNT162b2 vaccine, respectively.

Further, the team collected serum samples from individuals who had suffered breakthrough Omicron infections at two-time points. Accordingly, they collected samples after 14 days from symptom onset and 21 days from symptom onset.

Furthermore, the researchers used surface plasmon resonance (SPR) to test the binding of BA.4/5 and BA.2 RBDs to a panel of therapeutic antibodies. Lastly, the researchers used the neutralization data to place BA.3 and BA.4/5 on an antigenic map.

Study findings

Nutalai et al. have demonstrated that Omicron BA.1 infection following vaccination leads to induction of broadly neutralizing antibodies, with high titers against all the VOCs. In contrast, at the early time point, BA.4/5 titers were reduced 1.9-fold and 1.5-fold compared to BA.1 and BA.2, respectively. At the later time point, BA.4/5 titers were reduced 3.4-fold and two-fold compared to BA.1 and BA.2, respectively. The observations indicate that BA.4/5 escaped both the vaccine-induced and BA.1 infection-induced antibodies more than BA.1 and BA.2 sub-lineages.

SARS-CoV-2 variants BA.4 and BA.5 show substantial immune escape compared with BA.1 and BA.2 (4)

(Video) Europe, BA 5 and monkeypox next

Related Stories

  • Is there any impact of COVID-19 vaccines on the fertility of men and women of reproductive age?
  • Population-wide cohort study detects increase in major arterial and venous thrombotic events immediately after COVID-19 diagnoses
  • Research examines the roles of cytokines during SARS-CoV-2 infection in rhesus macaques

Pseudoviral neutralization assays of BA.4/5 by vaccine and BA.1 immune serum. IC50 values for the indicated viruses using serum obtained from vaccinees 28 days following their third dose of vaccine (A) AstraZeneca AZD AZD1222 (n=41), (B) 4 weeks after the third dose of Pfizer BNT162b2 (n=20). Serum from volunteers suffering breakthrough BA.1 infection volunteer taken (C) early ≤14 (n=12) days from symptom onset (median 13 days) (D) late ≥ 21 days from symptom onset (median 38 days) n=16. Comparison is made with neutralization titres to Victoria an early pandemic strain, BA.1, BA.1..1, BA.2 and BA.3. Geometric mean titres are shown above each column. The Wilcoxon matched-pairs signed rank test was used for the analysis and two-tailed P values were calculated.

In response to the AZD1222 vaccine, neutralization titers for BA.4/5 were reduced 2.1-fold compared to BA.1 and 1.8-fold compared to BA.2. Likewise, the BNT162b2 vaccination reduced neutralization titers by 3.2-fold compared to both BA.1 and BA.2. This data shows that while vaccine efficacy in preventing infection was low, particularly at a later time point as antibody titers wane, it protected progression towards severe disease.

Nutalai et al. also generated a panel of 28 potent human monoclonal antibodies from sera of Omicron cases. Of these, 10 mAbs neutralized BA.4/5 completely, while four other mAbs, Omi-09, 12, 29, and 35, showed a greater than five-fold reduction in the neutralization titer for BA.4/5 compared to BA.2. All the mAbs interacted with the RBD, except Omi-41, which bound the N-terminal domain (NTD). Therefore, it neutralized BA.1, BA.1.1, and BA.3 specifically but not BA.2 or BA.4/5.

SPR analysis confirmed a 1000-fold decrease in the sensitivity of Omi-12 against BA.4/5, an antibody sensitive to the F486V mutation. Likewise, SPR showed a 77-fold enhanced neutralization of BA.4/5 compared to BA.2 for Omi-32, an L452R sensitive antibody. The neutralizing activity of AZD1061 was similar against BA.4/5 and BA.2, while the REG10987, which partially neutralized BA.2, was further weakened against BA.4/5.

(Video) Doctor Mike Hansen - BA.4 and BA.5 causes more severe disease? - Covid Variant Update

The Omicron sub-lineages were clustered together on the antigenic map but remained far from earlier VOCs. Within the Omicron cluster, BA.4/5 was the most distant from the earlier sub-lineages, including BA.1 and BA.2.

Conclusions

The study data demonstrated that Omicron sub-lineages BA.4 and BA.5, compared to BA.1 and BA.2, escaped neutralization from sera of triple vaccinated individuals to a greater extent. Thus, a new or repeat wave of Omicron infection, driven by BA.4/5, is likely in the future. Moreover, the neutralizing activity of many mAbs was either knocked out or drastically impaired against BA.4/5 compared to BA.2.

Overall, the study highlighted that there is plenty of antigenic space for SARS-CoV-2 to explore, and so it may evolve along the Omicron lineage or to a new variant, e.g., Delta to Omicron. SARS-CoV-2 is unlikely to be stopped by COVID-19 vaccination, but next-generation vaccines or vaccines in combination with natural immunity will make people immune to this severe disease.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

  • Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum, Aekkachai Tuekprakhon, Jiandong Huo, Rungtiwa Nutalai, Aiste Dijokaite-Guraliuc, Daming Zhou, Helen M. Ginn, Muneeswaran Sekvaraj, Chang Liu, Alexander J. Mentzer, Piyada Supasa, Helen M. E. Duyvesteyn, Raksha Das, Donal Skelly, Thomas G Ritter, Ali Amini, Sagida Bibi, Sandra Adele, Sile Ann Johnson, Bede Constantinides, Hermione Webster, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Philip Goulder, OPTIC consortium, ISARIC4C consortium, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R. Screaton, bioRxiv pre-print 2022, DOI: https://doi.org/10.1101/2022.05.21.492554, https://www.biorxiv.org/content/10.1101/2022.05.21.492554v1
(Video) Overview of the BA.2 sub-lineage of the Omicron variant of the SARS-COV-2 virus

FAQs

Is it possible to get a COVID-19 reinfection? ›

Can you get Covid-19 twice? Yes, it is possible to get Covid-19 two, three or even more times. As new variants have emerged, and immunity from previous infection and immunisation has reduced over time, reinfection with Covid-19 has become increasingly common.

Can I develop immunity to COVID-19 after testing positive for PCR? ›

If you have previously tested positive for COVID-19, you will probably have developed some immunity to the disease. However, it cannot be guaranteed that everyone will develop immunity, or how long it will last. It is possible for PCR tests to remain positive for some time after COVID-19 infection.

When was the official name of SARS-CoV-2 announced? ›

On 11 February 2020, the International Committee on Taxonomy of Viruses adopted the official name "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2).

How long after receiving the COVID-19 booster are you protected? ›

Generally, people with healthy immune systems are protected from infection for three to four months after receiving a COVID booster, but protection from severe illness lasts eight months to a year.

What is a benefit of the COVID-19 autumn booster? ›

The autumn booster is being offered to those at high risk of the complications of COVID-19 infection, who may have not been boosted for a few months. As the number of COVID-19 infections increases over the winter, this booster should help to reduce your risk of being admitted to hospital with COVID-19.

How long does it take for COVID-19 booster to become effective? ›

It may take 7 days for a COVID-19 vaccine booster dose to work.

Can you take ibuprofen if you have the coronavirus disease? ›

Patients can take paracetamol or ibuprofen when self-medicating for symptoms of COVID-19, such as fever and headache, and should follow NHS advice if they have any questions or if symptoms get worse.

What is an antibody test for COVID-19? ›

An antibody test is a blood test to check if you've had coronavirus (COVID-19) before or been vaccinated.

Who issued the official name of COVID-19? ›

The official names COVID-19 and SARS-CoV-2 were issued by the WHO on 11 February 2020.

When was COVID-19 first reported? ›

On this website you can find information and guidance from WHO regarding the current outbreak of coronavirus disease (COVID-19) that was first reported from Wuhan, China, on 31 December 2019.

Where was COVID-19 first identified? ›

The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus was first identified in December 2019 in Wuhan, China.

Who might be at higher risk of becoming ill with COVID-19? ›

People who are at higher risk from COVID-19 and other respiratory infections include: Older people. Those who are pregnant. Those who are unvaccinated. People of any age whose immune system means they are at higher risk of serious illness. People of any age with certain long-term conditions.

Who are at higher risk of developing serious illness from COVID-19? ›

Older people, and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness.

How long does the virus that causes COVID-19 last on surfaces? ›

Recent research evaluated the survival of the COVID-19 virus on different surfaces and reported that the virus can remain viable for up to 72 hours on plastic and stainless steel, up to four hours on copper, and up to 24 hours on cardboard.

Can asymptomatic people transmit COVID-19? ›

Yes, infected people can transmit the virus both when they have symptoms and when they don't have symptoms. This is why it is important that all people who are infected are identified by testing, isolated, and, depending on the severity of their disease, receive medical care.

Are smokers more likely to develop severe disease with COVID-19? ›

Tobacco smoking is a known risk factor for many respiratory infections and increases the severity of respiratory diseases. A review of studies by public health experts convened by WHO on 29 April 2020 found that smokers are more likely to develop severe disease with COVID-19, compared to non-smokers.

What is the primary aim of the JCVI COVID-19 autumn booster programme? ›

The primary aim of the COVID-19 autumn booster programme is to increase immunity in those at higher risk of severe COVID-19 during winter 2022 to 2023. The Joint Committee on Vaccination and immunisation ( JCVI ) previously advised who would be offered a COVID-19 booster vaccine in autumn 2022.

What is the Yellow Card scheme for the COVID-19 vaccine? ›

The Yellow Card scheme is a mechanism by which anybody can voluntarily report any suspected adverse reactions or side effects to the vaccine. It is very important to note that a Yellow Card report does not necessarily mean the vaccine caused that reaction or event.

How long does it take to get the COVID-19 antibody test result? ›

You should get your result within 3 to 7 days of taking the test (usually by text or email).

Can you have the flu and COVID-19 at same time? ›

It's possible that the viruses that cause COVID-19 and the flu may spread in your community at the same time during the flu season. If this happens, people could become ill with one or both diseases at the same time. Testing can determine which virus you may have and help guide doctors to the appropriate treatment.

Are COVID-19 tests 100% reliable? ›

No test is 100% reliable, even those who meet regulatory standards for performance and safety. The results are also only relevant to that sample at that point in time.

What does a negative COVID-19 antibody test result mean? ›

A negative result means the test did not detect COVID-19 antibodies.

Are there any approved serological tests for detecting COVID-19 antibodies in the UK? ›

A number of laboratories and companies have developed serological tests, which detect antibodies produced by the body in response to infection. Several have been evaluated by Public Health England and approved for use in the UK.

When was the official name of SARS-CoV-2 announced? ›

On 11 February 2020, the International Committee on Taxonomy of Viruses adopted the official name "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2).

What is the origin of COVID-19? ›

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute respiratory syndrome coronavirus. It was first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan. All structural features of the novel SARS-CoV-2 virus particle occur in related coronaviruses in nature.

Which company designed the NHS COVID-19 app to protect the privacy and identity of the users? ›

This system is designed by Apple and Google to protect the privacy and identity of app users, making their use of the app anonymous.

Where was COVID-19 first identified? ›

The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus was first identified in December 2019 in Wuhan, China.

Where were first COVID-19 infections discovered? ›

The first known infections from SARS‐CoV‐2 were discovered in Wuhan, China. The original source of viral transmission to humans remains unclear, as does whether the virus became pathogenic before or after the spillover event.

When was COVID-19 first reported? ›

On this website you can find information and guidance from WHO regarding the current outbreak of coronavirus disease (COVID-19) that was first reported from Wuhan, China, on 31 December 2019.

Who issued the official name of COVID-19? ›

The official names COVID-19 and SARS-CoV-2 were issued by the WHO on 11 February 2020.

Can you take ibuprofen if you have the coronavirus disease? ›

Patients can take paracetamol or ibuprofen when self-medicating for symptoms of COVID-19, such as fever and headache, and should follow NHS advice if they have any questions or if symptoms get worse.

Are COVID-19 tests 100% reliable? ›

No test is 100% reliable, even those who meet regulatory standards for performance and safety. The results are also only relevant to that sample at that point in time.

How long does it take for COVID-19 booster to become effective? ›

It may take 7 days for a COVID-19 vaccine booster dose to work.

How long do COVID-19 booster side effects last? ›

Like all medicines, the COVID-19 vaccines can cause side effects, but not everyone gets them. Most side effects are mild and should not last longer than a week, such as: a sore arm from the injection.

How should you maintain social distancing to prevent the spread of COVID-19 at home with possible infection? ›

Spend as little time as possible in shared spaces such as kitchens, bathrooms and sitting areas. Avoid using shared spaces such as kitchens and other living areas while others are present and take your meals back to your room to eat. Observe strict social distancing.

How does COVID-19 usually spread? ›

When someone with a respiratory viral infection such as COVID-19 breathes, speaks, coughs or sneezes, they release small particles that contain the virus which causes the infection. These particles can be breathed in or can come into contact with the eyes, nose, or mouth.

How serious is COVID-19 usually for most children? ›

For most children and young people, these illnesses will not be serious, and they will soon recover following rest and plenty of fluids.

How can one stay physically active during COVID-19 self-quarantine? ›

Walk. Even in small spaces, walking around or walking on the spot, can help you remain active. If you have a call, stand or walk around your home while you speak, instead of sitting down.

Videos

1. New Omicron Variants Spreading - Contagious, Severity, Reinfection Risk - Can Reinfect After BA.5?
(Whiteboard Doctor)
2. September 1, 2022 ACIP Meeting - Booster Doses of Moderna; Pfizer/BioNTech COVID-19 Omicron-Modified
(Centers for Disease Control and Prevention (CDC))
3. Immune Escape By BA.4 and BA.5 Subvariants
(Drbeen Medical Lectures)
4. Live Q&A on COVID-19 variants of concern, including Omicron's sub-lineage BA.2
(World Health Organization (WHO))
5. Vaccines and Related Biological Products Advisory Committee – 6/28/2022
(U.S. Food and Drug Administration)
6. Omicron outcompetes omicron, official data
(Dr. John Campbell)

Top Articles

You might also like

Latest Posts

Article information

Author: Reed Wilderman

Last Updated: 11/28/2022

Views: 5889

Rating: 4.1 / 5 (52 voted)

Reviews: 91% of readers found this page helpful

Author information

Name: Reed Wilderman

Birthday: 1992-06-14

Address: 998 Estell Village, Lake Oscarberg, SD 48713-6877

Phone: +21813267449721

Job: Technology Engineer

Hobby: Swimming, Do it yourself, Beekeeping, Lapidary, Cosplaying, Hiking, Graffiti

Introduction: My name is Reed Wilderman, I am a faithful, bright, lucky, adventurous, lively, rich, vast person who loves writing and wants to share my knowledge and understanding with you.