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Virus World provides a daily blog of the latest news in the Virology field and the COVID-19 pandemic. News on new antiviral drugs, vaccines, diagnostic tests, viral outbreaks, novel viruses and milestone discoveries are curated by expert virologists. Highlighted news include trending and most cited scientific articles in these fields with links to the original publications. Stay up-to-date with the most exciting discoveries in the virus world and the last therapies for COVID-19 without spending hours browsing news and scientific publications. Additional comments by experts on the topics are available in Linkedin (https://www.linkedin.com/in/juanlama/detail/recent-activity/)
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Persistent Immune Imprinting Occurs After Vaccination with the COVID-19 XBB.1.5 mRNA Booster in Humans

Persistent Immune Imprinting Occurs After Vaccination with the COVID-19 XBB.1.5 mRNA Booster in Humans | Virus World | Scoop.it

Highlights

  • XBB.1.5 COVID-19 mRNA vaccine elicits neutralizing antibodies against current variants
  • Depletion of Wuhan-Hu-1 S-reactive plasma antibodies abrogate XBB.1.5 neutralization
  • XBB.1.5 COVID-19 mRNA vaccine primary recalls Wuhan-Hu-1 S-reactive memory B cells

Summary

Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures to antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA vaccination rather than priming Omicron-specific naive B cells. These findings indicate that immune imprinting occurs after repeated Wuhan-Hu-1 spike exposures, but whether it can be overcome remains unclear.
 
To understand the persistence of immune imprinting, we investigated memory and plasma antibody responses after administration of the updated XBB.1.5 COVID-19 mRNA vaccine booster. We showed that the XBB.1.5 booster elicited neutralizing antibody responses against current variants that were dominated by recall of pre-existing memory B cells previously induced by the Wuhan-Hu-1 spike. Therefore, immune imprinting persists after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 booster vaccination, which will need to be considered to guide future vaccination.
 
Published in Immunity (March 14, 2024):
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Early COVID-19 Vaccine Effectiveness of XBB.1.5 Vaccine Against Hospitalization and ICU Admission, The Netherlands - medRxiv

Early COVID-19 Vaccine Effectiveness of XBB.1.5 Vaccine Against Hospitalization and ICU Admission, The Netherlands - medRxiv | Virus World | Scoop.it

We present early vaccine effectiveness (VE) estimates of the 2023 seasonal COVID-19 vaccination campaign using XBB.1.5 vaccine against COVID-19 hospitalization and ICU admission in previously vaccinated adults ≥60 years old in the Netherlands. We compared vaccination status of 2050 hospitalizations including 92 ICU admissions with age group-, sex-, region- and date-specific population vaccination coverage between 9 October and 5 December 2023. VE against hospitalization was 70.7% (95% CI: 66.6; 74.3), VE against ICU admission was 73.3% (95% CI: 42.2; 87.6).

 

Preprint in medRxiv (Dec. 13, 2023):

https://doi.org/10.1101/2023.12.12.23299855 

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Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines - medRxiv

Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines - medRxiv | Virus World | Scoop.it

Background: Subvariants of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) omicron XBB-lineage have the potential to escape immunity provided by prior infection or vaccination. For Covid-19 immunizations beginning in the Fall 2023, the U.S. FDA has recommended updating to a monovalent omicron XBB.1.5-containing vaccine. 

 

Methods: In this ongoing, phase 2/3 study participants were randomized 1:1 to receive 50-µg doses of mRNA-1273.815 monovalent (50-µg omicron XBB.1.5 spike mRNA) or mRNA-1273.231 bivalent (25-µg omicron XBB.1.5 and 25-µg omicron BA.4/BA.5 spike mRNAs) vaccines, administered as 5th doses, to adults who previously received a primary series and 3rd dose of an original mRNA coronavirus disease 2019 (Covid-19) vaccine, and a 4th dose of a bivalent (omicron BA.4/BA.5 and original SARS-CoV-2) vaccine. Interim safety and immunogenicity data 15 days post-vaccination are presented. 

 

Results: In April 2023, participants received mRNA-1273.815 (n=50) and mRNA-1273.231 (n=51). The median intervals from the prior dose of BA.4/BA.5-containing bivalent vaccine were 8.2 and 8.3 months for the mRNA-1273.815 and mRNA-1273.231 groups, respectively. Both vaccines increased neutralizing antibody (nAb) geometric mean titers against all variants tested at day 15 post-booster nAb compared to pre-booster levels. Geometric mean fold-rises from pre-booster titers after the monovalent booster were numerically higher against XBB.1.5, XBB.1.16 and SARS-CoV-2 (D614G) than those of the bivalent booster and were comparable against BA.4/BA.5 and BQ1.1 variants for both vaccines. The monovalent vaccine also elicited nAb responses against omicron XBB.2.3.2, EG.5.1, FL.1.5.1 and BA.2.86 that were similar to those against XBB.1.5 in a subset (n=20) of participants. The occurrence of solicited adverse reactions and unsolicited adverse events were overall similar to those previously reported for the original mRNA-1273 50-µg and omicron BA.4/BA.5-containing bivalent mRNA-1273 vaccines. 

 

Conclusion: In this interim analysis, XBB.1.5-containing monovalent and bivalent vaccines elicited potent neutralizing responses against variants of the omicron XBB-lineage (XBB.1.5, XBB.1.6, XBB.2.3.2, EG.5.1, and FL.1.5.1) as well as the recently emerged BA.2.86 variant. The safety profile of the XBB.1.5-containing vaccine was consistent with those of prior vaccines. These results overall indicate that the XBB.1.5-containing mRNA-1273.815 vaccine has the potential to provide protection against these emerging variants and support the Covid-19 vaccine update in 2023-2024 to a monovalent XBB.1.5-containing vaccine.

 

Preprint avilable in medRxiv (Sept. 7, 2023):

https://doi.org/10.1101/2023.08.22.23293434 

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China Approves the World's First Vaccine against XBB Descendent Lineages of SARS-CoV-2 for Emergency Use

China Approves the World's First Vaccine against XBB Descendent Lineages of SARS-CoV-2 for Emergency Use | Virus World | Scoop.it

CHENGDU, China, June 8, 2023 /PRNewswire/ -- On June 8th, 2023, Coviccine® Trivalent XBB.1.5-Recombinant COVID-19 Trivalent (XBB.1.5+BA.5+Delta) Protein Vaccine (Sf9 cell) developed by WestVac BiopharmaWest China Medical CenterSichuan University was approved for EUA by relevant authorities in China. This is the first COVID-19 vaccine in the world approved for EUA against XBB descendent lineages of SARS-CoV-2. It demonstrates that China is leading the world in the development of COVID-19 vaccines. WestVac Biopharma and its subsidiary company WestVac Biopharma (Guangzhou) leveraged the rapid response of the insect cell expression platform on constructing the vector for Coviccine® Trivalent XBB.1.5-Recombinant COVID-19 Trivalent (XBB.1.5+BA.5+Delta) Protein Vaccine (Sf9 Cell), which is of high purity and high quality for human use. The subunit vaccine antigen is precisely designed based on the structure of the targeting S-RBD and HR proteins of the COVID-19 subvariants XBB.1.5 and BA.5 and self-assembled into stable trimeric protein particles with squalene-based oil-in-water emulsion adjuvant added after purification and mixing. This novel adjuvant significantly raises the titer of neutralizing antibodies, which enables the trimeric protein vaccine to induce a higher level T-cell immune response. Studies have shown that Coviccine® Trivalent XBB.1.5 induced a high titer of neutralizing antibodies against multiple subvariants, including Omicron subvariants XBB.1.5, XBB1.16, XBB1.9.1, XBB.2.3, BA.5, BF.7, BQ.1, BA.2.75. 14 days after injection of this product, the protective efficacy against XBB.1, XBB.1.5, XBB1.9 is 93.28% with an excellent safety profile, demonstrating that it is a broad-spectrum COVID-19 vaccine against multiple prevalent subvariants locally and internationally.

 

The XBB.1.5 variant had gradually become the major circulating variant in various parts of the world by the beginning of 2023. With the professional guidance and support from the State Council's Joint Prevention and Control Mechanism's vaccine R&D team, the scientific team of WestVac Biopharma/West China Medical Center, Sichuan University overcame all hurdles and successfully developed a vaccine covering XBB family of variants. Early May, China CDC expert noticed that the transmission and immune escape capability of XBB variants is much stronger than that of the early circulating Omicron variants. The XBB.1 descendent lineages currently predominate SARS-CoV-2 circulation globally. As of the end of May, XBB family of variants accounted for 98.1% of all variants in the United States. In China, newly detected XBB variants have increased gradually and now exceed 90%. The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) advised on May 18 that new formulations of COVID-19 vaccines should aim to induce antibody responses that neutralize XBB descendent lineages. The rate of "second infection" is rising. Experts urge prompt prevention, immunization against COVID-19, particularly for people with high-risk infection, the elderly, people with underlying diseases and those who are immunocompromised to get a vaccine covering SARS-CoV-2 variants. WestVac Biopharma uses the international advanced insect cell recombinant protein vaccine platform to develop Coviccine® Trivalent XBB.1.5 which has been approved for EUA in China. WestVac's COVID-19 vaccine offers a unique option for COVID-19 prevention, is crucial for the prevention of the current XBB descendent lineages and contributes significantly to the ongoing management of the COVID-19 epidemic.

 

About WestVac Biopharma

 

WestVac Biopharma Co., Ltd. is an innovative biopharmaceutical company, capable of doing the full spectrum of research, manufacturing, and commercialization of products. WestVac Biopharma has been selected successfully on the list of unicorn companies from 2021 to 2023. WestVac Biopharma Co., Ltd. is located in Chengdu of West China while WestVac Biopharma (Guangzhou), a wholly-owned subsidiary company of WestVac Biopharma., is located in Guangzhou Economic Development Zone. WestVac Biopharma Co., Ltd. has completed construction of 5,000-litre and 3,000-litre insect cell recombinant protein vaccine production lines with an annual production capacity of 100 million doses. The GMP production lines were well established with the "Drug Production License" in place. WestVac Biopharma (Guangzhou) has completed scale-up construction of insect cell recombinant protein vaccine production lines with an annual production capacity of 100 million doses. In December 2022, Coviccine®-Recombinant COVID-19 Vaccine (Sf9 cell) developed by WestVac Biopharma was approved by relevant authorities for EUA in China.

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Here's How Effective the Latest COVID-19 Shots Are for Adults | MedPage Today

Here's How Effective the Latest COVID-19 Shots Are for Adults | MedPage Today | Virus World | Scoop.it

Effectiveness of the 2023-2024 vaccine lands at 54% for symptomatic cases. The updated 2023-2024 COVID-19 vaccine was approximately 54% effective against symptomatic SARS-CoV-2 infection in adults, and was also effective against the JN.1 variant, which became predominant in January, CDC researchers said. Overall, vaccine effectiveness against symptomatic COVID was 57% for people ages 18 to 49 years and 46% for people ages 50 and older, reported Ruth Link-Gelles, PhD, of the CDC's National Center for Immunization and Respiratory Diseases, and colleagues in the Morbidity and Mortality Weekly Reportopens in a new tab or window.

 

The updated vaccine is a monovalent XBB.1.5-derived vaccine, and there have been few estimates regarding its effectiveness, the authors noted. This study is the first to look at the vaccine's effectiveness against symptomatic COVID caused by the JN.1 variantopens in a new tab or window, a derivative of BA.2.86. The data came from the CDC's Increasing Community Access to Testing program that provided no-cost SARS-CoV-2 nucleic acid amplification tests (NAAT) to uninsured people at participating CVS and Walgreens pharmacies from Sept. 21, 2023 to Jan. 14, 2024. Vaccine effectiveness was 58% among those who received testing 7 to 59 days after receiving the updated vaccine, and 49% among those who received testing 60 to 119 days after receipt.

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FDA Takes Action on Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants - FDA

FDA Takes Action on Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants - FDA | Virus World | Scoop.it

Today, the U.S. Food and Drug Administration took action approving and authorizing for emergency use updated COVID-19 vaccines formulated to more closely target currently circulating variants and to provide better protection against serious consequences of COVID-19, including hospitalization and death. Today’s actions relate to updated mRNA vaccines for 2023-2024 manufactured by ModernaTX Inc. and Pfizer Inc. Consistent with the totality of the evidence and input from the FDA’s expert advisors, these vaccines have been updated to include a monovalent (single) component that corresponds to the Omicron variant XBB.1.5.

 

What You Need to Know

  • Individuals 5 years of age and older regardless of previous vaccination are eligible to receive a single dose of an updated mRNA COVID-19 vaccine at least 2 months since the last dose of any COVID-19 vaccine. 
  • Individuals 6 months through 4 years of age who have previously been vaccinated against COVID-19 are eligible to receive one or two doses of an updated mRNA COVID-19 vaccine (timing and number of doses to administer depends on the previous COVID-19 vaccine received). 
  • Unvaccinated individuals 6 months through 4 years of age are eligible to receive three doses of the updated authorized Pfizer-BioNTech COVID-19 Vaccine or two doses of the updated authorized Moderna COVID-19 Vaccine.
  • The FDA is confident in the safety and effectiveness of these updated vaccines and the agency’s benefit-risk assessment demonstrates that the benefits of these vaccines for individuals 6 months of age and older outweigh their risks.
  • Individuals who receive an updated mRNA COVID-19 vaccine may experience similar side effects as those reported by individuals who previously received mRNA COVID-19 vaccines as described in the respective prescribing information or fact sheets.
  • The updated vaccines are expected to provide good protection against COVID-19 from the currently circulating variants. Barring the emergence of a markedly more virulent variant, the FDA anticipates that the composition of COVID-19 vaccines may need to be updated annually, as is done for the seasonal influenza vaccine. 
  • The U.S. Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet tomorrow (Sept. 12), to discuss clinical recommendations on who should receive an updated vaccine, as well as further considerations for specific populations such as immunocompromised and older individuals. 
  • Manufacturers have publicly announced that the updated vaccines would be ready this fall, and the FDA anticipates that the updated vaccines will be available in the near future.
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SARS-CoV-2 Neutralizing Antibodies Following a Second BA.5 Bivalent Booster - bioRxiv

SARS-CoV-2 Neutralizing Antibodies Following a Second BA.5 Bivalent Booster - bioRxiv | Virus World | Scoop.it

Bivalent COVID-19 mRNA vaccines expressing both the ancestral D614G and Omicron BA.5 spike proteins were introduced in August 2022 with the goal of broadening immunity to emerging SARS-CoV-2 Omicron subvariants. Subsequent studies on bivalent boosters found neutralizing antibody responses similar to boosters with the original monovalent vaccine, likely the result of immunological imprinting. Guidelines allow for administration of a second bivalent booster in high-risk groups, but it remains unknown whether this would broaden antibody responses.

 

To address this question, we assessed longitudinal serum SARS-CoV-2-neutralizing titers in 18 elderly immunocompetent individuals (mean age 69) following a fourth monovalent booster and two BA.5 bivalent booster vaccines using pseudovirus neutralization assays against D614G, Omicron BA.5, and Omicron XBB.1.5. There was a small but significant increase in peak neutralizing antibody responses against Omicron BA.5 and XBB.1.5 following the first bivalent booster, but no significant increase in peak titers following the second bivalent booster. Omicron-specific neutralizing titers remained low after both doses of the BA.5 bivalent booster. Our results suggest that a second dose of the BA.5 bivalent booster is not sufficient to broaden antibody responses and to overcome immunological imprinting. A monovalent vaccine targeting only the spike of the recently dominant SARS-CoV-2 may mitigate the back boosting associated with the original antigenic sin.

 

Preprint at bioRxiv (August 14, 2023):

 https://doi.org/10.1101/2023.08.13.553148 

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Could New Omicron Variant XBB.1.5 Fuel Further Covid Infections? -  The Guardian

Could New Omicron Variant XBB.1.5 Fuel Further Covid Infections? -  The Guardian | Virus World | Scoop.it

The offshoot accounts for 40% of Covid cases in the US, raising fears of fresh waves of illness as it spreads to other countries. Scientists have raised concerns about a new Covid variant that is spreading fast in the US and threatening to cause further waves of infection. Here’s what we know so far.

 

What is the new variant called?


It’s known as XBB.1.5. It’s one of the latest descendants of Omicron, the highly transmissible version of Covid that caused cases to surge in the UK last winter. Offshoots of Omicron have dominated global Covid infections ever since. XBB.1.5 evolved from the XBB variant of Omicron, itself a fusion of two different BA.2 variants.

 

How fast is it spreading?


The variant seems to have arisen in or around New York state in late October. At the end of December, the number of cases in the US more than doubled in a week. It now accounts for about 40% of all Covid infections in the US. Hospitalisations are rising in New York, raising fears that XBB.1.5 is about to cause further waves of illness as it spreads to other countries. Some US estimates suggest that XBB.1.5 is spreading more than twice as fast as the BQ.1.1 variant, which is one of the most common variants found in the UK.

 

Why is it spreading so rapidly?


The variant has an unusual mutation known as F486P that is helping it spread. The mutation changes part of the Covid virus that many antibodies from vaccination or previous infection target. The change makes the antibodies less effective at neutralising the virus. The parent variant, XBB, has a different mutation at the same position. This makes XBB good at evading immune defences too, but the mutation comes with a cost: the virus cannot latch on to human cells as effectively, so the virus is actually less infectious. The XBB.1.5 offshoot suffers no such handicap: the F486P mutation allows it to evade antibodies without compromising how well it attaches to human cells. In fact, it binds to them even more strongly than XBB, driving up its infectivity. “The mutation can give that immune evasion without the cost to infectivity and that’s why it’s become so successful,” says Ravi Gupta, professor of clinical microbiology at the University of Cambridge.

 

Has the virus reached the UK?


Scientists in the UK analyse the genetics of only a fraction of Covid samples now, so there’s some uncertainty around XBB.1.5. But the variant has been detected here, and surveillance suggests it makes up at least 4% of Covid viruses being sequenced.

 

Does it cause more severe disease?

 

There is no evidence that XBB.1.5 causes more severe disease than other Omicron variants. But the fact that it is spreading fast is worrisome, as the virus is more likely to reach vulnerable people who could be hospitalised or die from the infection, especially if they have not received their latest booster.

 

Will it spark another wave?


That is the concern. In the US, scientists suspect XBB.1.5 is at least partly responsible for the rise in hospital admissions in New York, though cold weather and indoor gathering will also contribute. It is unclear whether the variant will drive a big surge in the UK, but some rise is anticipated. “It might drive an increase in cases, but I’m not convinced this will necessarily cause an explosive wave of infections in the UK,” says Gupta. “I don’t think there’s any cause to panic. The main thing we worry about is the severity of the disease, and there is no evidence that it’s more severe. People should, however, make sure they are up to date with their vaccines.” Paradoxically, the winter wave of influenza and other nasty respiratory viruses that are doing the rounds might blunt any spike in Covid. If you catch a virus it should activate the innate immune system, the body’s frontline defences against pathogens, offering at least some protection against viruses that follow soon after. So if you caught flu or another respiratory virus over Christmas, your immune defences might resist a brief encounter with Covid.

 

What do scientists advise?


Vaccines are still the best way to protect against severe Covid, but Sam Wilson, a professor of virology at the University of Glasgow, says taking familiar Covid precautions will also help. “Regardless of the impact of a new variant, the NHS is already under tremendous pressure from a cocktail of different viruses this winter,” he says. “Where it is possible, taking voluntary steps to reduce transmission – reducing contacts, wearing high-quality masks in crowded indoor spaces, and isolating if you have symptoms – will help reduce the pressure on the NHS.”