Tag: Delta variant

Second J&J Dose Needed for Delta Variant

Photo by Ivan Diaz on Unsplash

Johnson & Johnson’s COVID vaccine is much less effective against the Delta and Lambda variants than against the original wild-type virus, according to a new study posted on the BioRxiv preprint server on Tuesday.

Though a cause for concern, the results come from in vitro tests, and may not reflect the real world vaccine performance. However, the authors said this adds to evidence that the 13 million people inoculated with the J&J vaccine may need a second dose, preferably an mRNA vaccine, the authors said.
The findings, which are still to be peer reviewed, are however consistent with observations that a single dose of the AstraZeneca vaccine, which is similar to the J&J one, shows only about 33 percent efficacy against developing symptoms with the Delta variant.

“The message that we wanted to give was not that people shouldn’t get the J&J vaccine, but we hope that in the future, it will be boosted with either another dose of  J&J or a boost with Pfizer or Moderna,” said study leader Nathaniel Landau, a virologist at NYU’s Grossman School of Medicine.

Other experts said the results are what they would have expected, because all of the vaccines seem to work better when given in two doses. “I have always thought, and often said, that the  J&J vaccine is a two-dose vaccine,” said John Moore, a virologist at Weill Cornell Medicine in New York.

Dr Moore pointed to several studies in monkeys and people that have shown greater efficacy with two doses of the J&J vaccine, compared with one dose. The new study was particularly credible, he said, because it was published by a team not linked to any vaccine manufacturer.

But the data from the new study “do not speak to the full nature of immune protection,” said Seema Kumar, a spokeswoman for J&J. “Studies sponsored by the company indicate that the vaccine “generated strong, persistent activity against the rapidly spreading Delta variant,” she said.

The Delta variant is the most transmissible of the SARS-CoV-2 variants, and has become dominant in South Africa. 

Several studies have suggested that the mRNA vaccines made by Pfizer-BioNTech and Moderna will maintain their efficacy against the coronavirus, including all variants identified so far. One recent study showed, for example, that the vaccines trigger a persistent immune reaction in the body that may protect against the coronavirus for years. The J&J vaccine is newer, and has had fewer studies.

The J&J vaccine has had reports of rare blood clots and extremely rare neurological disorders, as well as problems with contamination at a US manufacturing plant. This is still not as bad as the disastrous news that the AstraZeneca vaccine was virtually ineffective against the Beta variant which was then the dominant strain in South Africa.

Small studies by J&J affiliated researchers suggested that the vaccine was only slightly less effective against the Delta variant than against the wild-type virus, and that antibodies stimulated by the vaccine grew in strength over eight months.

Dr Dan Barouch, a virologist at Beth Israel Deaconess Medical Center in Boston said it was important to consider the vaccine’s strength over time.

“Fundamentally I don’t see that there’s any discordance,” he said. “The question is that of kinetics, it’s not just magnitude, because immune responses are not static over time.” The new study also did not consider other components of immune defence, he added.

Dr Landau and his colleagues had compared blood samples taken from 17 people who had two doses of an mRNA vaccine and 10 who had one J&J vaccine dose.

The  J&J vaccine started out with a lower efficacy than the mRNA vaccines and showed a bigger drop in efficacy against the Delta and Lambda variants. “The lower baseline means that what’s left to counter Delta is very weak,” Dr Moore said. “That is a substantial concern.”

Very few vaccines are given as a single dose, because the second dose is needed to amp up antibody levels, noted Akiko Iwasaki, an immunologist at Yale University. People who were inoculated with the J&J vaccine “are relying on that primary response to maintain high levels of antibodies, which is difficult, especially against the variants,” she said.

Boosting immunity with a second dose should raise the antibody levels high enough to counter the variants, she said.

Source: New York Times

As Gauteng Weathers Third Wave, Western Cape Readies its Defences

Image by Quicknews

While COVID infection rates in Gauteng remain high, Western Cape is now firmly in a third wave, with an average of 1969 new cases a day. The healthcare system there has been monitoring the situation and preparing for the expected surge in cases.

“We are in a steep third wave, driven by the Delta variant and urge everyone to adhere strictly to protective behaviours, as a key drive to contain it. We anticipate that the third wave could be as high as the second wave. We await revised modelling from the SACMC to re-calibrate our response,” said head of health Dr Keith Cloete. Data on cases, healthcare capacity and details of the Western Cape’s responses were made available on the SA Coronavirus Portal.

In the Western Cape, the reproductive number has been over one for the past two months and is currently sitting at approximately 1.2, meaning an acceleration of new cases. The test positivity rate is at about 32%.

The public and private sector are using around two-thirds of the oxygen production capacity of Afrox’s plant. The level 4 restrictions with their accompanying alcohol ban saw a significant drop in week-on-week trauma presentations (~25%) and weekend trauma burden (~33% drop). This comes even with the context typical end of month increase as well as expected remaining alcohol stock, demonstrating the ban’s effectiveness.

The modelling referred to by Dr Cloete currently shows a high of ~500 daily admissions by 17 July, however an updated model is awaited. Public sector COVID bed capacity is being increased by converting beds and opening field hospitals, with a planned capacity of 2300 beds.

About 48.5% and 10.4% of the Western Cape population aged 60+ and 50-59 respectively have been vaccinated so far. Meanwhile, in a media briefing on Friday, Acting Health Minister Mmamoloko Kubayi-Ngubane announced that COVID vaccine registration for South Africans between the ages of 35-49 will open on July 15, with vaccinations for this age group planned to commence on August 1.

Preliminary Study Explains Why Delta Variant is So Infectious

Colorized scanning electron micrograph of an apoptotic cell (purple) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

A preliminary study has possibly determined why the SARS-CoV-2 Delta variant is more infectious and pathogenic than its ancestor.

Through a series of in vitro experiments, researchers have discovered that variant’s enhanced ability to induce cell-to-cell fusion (syncytia) and reduced susceptibility to vaccine and infection-induced antibodies together help make the Delta variant more infectious than previously circulating variants. The study, which is yet to be peer reviewed, is currently available on the bioRxiv preprint server.

The SARS-CoV-2 virus has undergone more than 12 000 mutations since it was first detected in December 2019, most of which are neutral and do not contribute to viral evolution. However, the acquisition of specific mutations in structural and non-structural proteins has caused the emergence of novel, more virulent SARS-CoV-2 variants.

Spike protein mutations are particularly concerning as they can significantly influence viral infectivity, virulence, and immune evasion ability.

The B.1.617 lineage drove a massive surge in new COVID cases in India. This lineage is further divided into three sub-lineages, namely B.1.617.1, B.1.617.2, and B.1.617.3. Although these emerged first in India, the B.1.617.2 or Delta variant or soon became dominant in many countries, including South Africa where it has driven a new surge of infections, particularly in Gauteng Province. The World Health Organization (WHO) has designated the Delta variant as a ‘Variant of Concern’ (VOC) due to its significantly increased infectivity and pathogenicity.

In the current study, the scientists have evaluated the susceptibility of the Delta variant to neutralisation by vaccine or natural infection-induced antibodies.

Delta variant mutations 

The Delta variant’s spike protein contains nine mutations in the S1 subunit and one mutation in the S2 subunit. In the S1 subunit, five mutations are present in the N-terminal domain containing binding sites (epitopes) for neutralising antibodies. In addition, two mutations are present in the receptor-binding domain of the S1 subunit, which is known to influence antibody-mediated neutralisation and infectivity. Among the three remaining mutations, two are known to increase angiotensin-converting enzyme 2 (ACE2) binding, viral replication, and spike protein cleavage at the S1/S2 site.    

Delta variant host cell entry

Using African green monkey and human cells, the researchers found that Delta can enter kidney cells of both species with similar efficacy as the wild-type SARS-CoV-2. However, for human colon and lung cells, Delta showed 1.5-fold and 2-fold higher invading ability, respectively, compared to the wild-type virus. Since the Delta variant spike protein did not exhibit increased ACE2 binding, the scientists suggest that increased entry of B.1.617.2 into colon and lung cells is not mediated by enhanced ACE2 binding.

Besides inducing fusion between the viral envelope and host cell membrane, the spike protein triggers the fusion of infected cells with nearby cells to form large multinucleated cells, known as syncytia. Given the fact that spike-induced syncytia formation contributes to COVID pathogenesis, the scientists investigated whether Delta variant infection is associated with increased syncytia formation.

By conducting in vitro experiments on human lung cells expressing high levels of ACE2, they found that Delta spike expression leads to 2.5-fold higher and larger syncytia formation than the wild-type spike expression.

Delta variant’s immune evasion ability less than Beta?

The scientists tested the ability of four therapeutic monoclonal antibodies to neutralise the Delta variant, of which only Bamlanivimab failed. The other three antibodies exhibited similar efficacy in neutralising both wild-type virus and Delta variant.

Antibodies derived from COVID recovered patients, and BNT162b2-vaccinated individuals showed only slightly reduced efficacy in neutralising the Delta variant as compared to the wild-type virus. In contrast, the B.1.315 or Beta variant, first detected in South Africa, showed a significantly higher ability to evade infection- and vaccination-induced immunity.

In summary

The study showed that Delta’s increased ability to invade lung cells may enhance infectivity and pathogenicity. Though it has lower susceptibility to antibody-mediated neutralisation, it is possible that Delta may be effectively controlled by immunity developed in response to natural infection or vaccination.

Source: News-Medical.Net

Journal information: Arora P. 2021. Increased lung cell entry of B.1.617.2 and evasion of antibodies induced by infection and BNT162b2 vaccination. bioRxiv. https://www.biorxiv.org/content/10.1101/2021.06.23.449568v1