Oxford/AstraZeneca COVID Shot Less Effective Against South African Variant

 British drugmaker AstraZeneca said on Saturday its vaccine developed with the University of Oxford appeared to offer only limited protection against mild disease caused by the South African variant of COVID-19, based on early data from a trial.

The study from South Africa's University of the Witwatersrand and Oxford University showed the vaccine had significantly reduced efficacy against the South African variant, according to a Financial Times report published earlier in the day.

Among coronavirus variants currently most concerning for scientists and public health experts are the so-called British, South African and Brazilian variants, which appear to spread more swiftly than others.

"In this small phase I/II trial, early data has shown limited efficacy against mild disease primarily due to the B.1.351 South African variant," an AstraZeneca spokesman said in response to the FT report.

The newspaper said none of the more than 2,000 trial participants had been hospitalised or died.

"However, we have not been able to properly ascertain its effect against severe disease and hospitalisation given that subjects were predominantly young healthy adults," the AstraZeneca spokesman said.

The company said it believed its vaccine could protect against severe disease, given that the neutralising antibody activity was equivalent to that of other COVID-19 vaccines that have demonstrated protection against severe disease.

The trial, which involved 2,026 people of whom half formed the placebo group, has not been peer-reviewed, the FT said.

While thousands of individual changes have arisen as the virus mutates into new variants, only a tiny minority are likely to be important or change the virus in an appreciable way, according to the British Medical Journal.

"Oxford University and AstraZeneca have started adapting the vaccine against this variant and will advance rapidly through clinical development so that it is ready for Autumn delivery should it be needed," the AstraZeneca spokesman said.

On Friday Oxford said their vaccine has similar efficacy against the British coronavirus variant as it does to the previously circulating variants.

https://www.usnews.com/news/top-news/articles/2021-02-06/oxford-astrazeneca-covid-shot-less-effective-against-south-african-variant-study

Cautionary note on recall vaccination in ex-COVID-19 subjects

 Riccardo Levi, Elena Azzolini,  

View ORCID ProfileChiara Pozzi, Leonardo Ubaldi, Michele Lagioia, Alberto Mantovani,  View ORCID ProfileMaria Rescigno

doi: https://doi.org/10.1101/2021.02.01.21250923

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.02.01.21250923v1.full.pdf

Abstract

Currently approved COVID-19 vaccines based on mRNA or adenovirus require a first jab followed by recall immunization. There is no indication as to whether individuals who have recovered from COVID-19 should be vaccinated, and if so, if they should receive one or two vaccine doses. Here, we tested the antibody response developed after the first dose of the mRNA based vaccine encoding the SARS-CoV-2 full-length spike protein (BNT162b2) in 124 healthcare professionals of which 57 had a previous history of COVID-19 (ExCOVID). Post-vaccine antibodies in ExCOVID individuals increase exponentially within 7-15 days after the first dose compared to naïve subjects (p<0.0001). We developed a multivariate Linear Regression (LR) model with l2 regularization to predict the IgG response for SARS-COV-2 vaccine. We found that the antibody response of ExCOVID patients depends on the IgG pre-vaccine titer and on the symptoms that they developed during the disorder, with anosmia/dysgeusia and gastrointestinal disorders being the most significantly positively correlated in the LR. Thus, one vaccine dose is sufficient to induce a good antibody response in ExCOVID subjects. On the contrary, a second dose might switch-off the immune response due to antigen exhaustion, which occurs in response to several viruses or drive the development of low-affinity antibodies for SARS-CoV-2 which may foster an antibody dependent enhancement (ADE) reaction when re-exposed to the virus. These results question whether a second shot in ExCOVID subjects is indeed required and suggest to post-pone it while monitoring antibody response longevity.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was partially supported by a philantropic donation by Dolce & Gabbana, by the Italian Ministry of Health (Ricerca corrente) and by Fondazione Humanitas per la Ricerca.

https://www.medrxiv.org/content/10.1101/2021.02.01.21250923v1

Adenovirus-Vector Vaccine Roundup, Feb 5: Sputnik and More

 By Derek Lowe 

We’ve had yet more news in this area in the ten days or so since my last vaccine news roundup post, so here’s a look at the current situation. Most all the news has been in the viral vector area, so I’ll stick to that this time around.

The big news here is the publication of the Gamaleya Institute’s “Sputnik-V” vaccine data. In the end, we have data on about 15,000 patients who were vaccinated, and on about 5,000 in the placebo control group. Volunteers got a dose of an adenovirus-26 vector vaccine, followed 21 days later by a dose of the identical construct in an adenovirus-5 vector. This is to try to avoid the immune response to the vector itself, which has always been a concern with any of the viral-vector vaccines (against the coronavirus and against anything else!) Another concern is the possibility that once you’ve had such an adenovirus-vector treatment, that you might be in trouble for further vaccinations that use the same vector (and this remains an open question).

Counting from the day of the second dose, there were 16 cases of disease in the vaccinated cohort, and 62 cases in the controls. That comes out to a two-dose vaccine efficacy of 91.6%, with a 95% confidence interval of 85.6% to 95.2%. In no subgroup (age, gender, etc.) was it lower than 87%. As with most of the other trials, this is largely based on symptomatic disease – the participants were checked by PCR at the beginning and on the day of the second dose, but at no other times. Importantly, and in line with the other vaccine trial data we’ve seen so far, there were no cases at all of moderate or severe disease in the vaccinated group after the date of the second dose. Figure 2 of the paper shows that the effect of the first shot kicks in around day 16-18 – a bit longer than what’s been seen with the mRNA vaccines, but the curve afterwards shows the same strong protection. Safety looks good, with few adverse events and nothing serious connected with the vaccine itself.

So these data look strong, strong enough that a single-dose trial is underway as well (and that will make an interesting comparison with J&J’s Ad26-vector vaccine, for which we have single-dose data with a two-dose trial underway). We’ll be getting more real-world data on this one, as it’s being deployed in several countries, and it will certainly be worth seeing how it handles the variant strains that we’re seeing now. My expectation is that it will deal with the B.1.1.7 one at nearly the same efficacy and drop down to the 50-60% efficacy range against the B.1.351 strain, as has been seen with the other vaccines where we have such data. Based on the numbers we have, I see no reason why this vaccine can’t make a solid contribution to fighting the pandemic, and I’m very glad to have another efficacious one out there for use.

For updates on the Oxford/AstraZeneca vaccine, I’ll refer everyone to this post, and likewise for updates on the J&J vaccine, this recent post. As for the CanSino Ad5 vaccine, there are reports in Chinese media of positive safety and efficacy data, which means that it’s officially moving into Phase III. That sounds a bit odd, considering that it’s apparently being offered in Pakistan, Malaysia, and other countries already, but these are odd times. There is also word of a combination trial with this one and the Sputnik vaccine as well, which would replace the second (Ad5) dose of the former with the CanSino one. And the AstraZeneca/Gamaleya combination trial was reported just today as ready to start in Azerbaijan and a whole list of other countries.

Of the other viral vectors I reported on in the most recent post, the big news has been on the Vaxart oral candidate. Unfortunately, the company reported that they were unable to detect serum neutralizing antibodies in most trial subjects, which has to be considered an unwelcome development. Their press release sounds a lot more positive than that (as is so often the case), but it’s rather light on actual data. It may be (although it seems less likely) that the real-world efficacy of this candidate will depend on its mucosal immunogenicity and that the lack of neutralizing antibodies in serum is a red herring, but the only way to convince people of that will be with lots of strong efficacy data in human trials.

The Reithera vaccine has had a news report about being available in Italy in September, but on closer inspection it’s “if the Phase II and Phase III trials, which haven’t started yet, go well”, so that’s not too useful. And the Washington Univ./Bharat Biotech intranasal adenovirus vector candidate is set to go into Phase I trials on 75 people in India.

https://blogs.sciencemag.org/pipeline/archives/2021/02/05/adenovirus-vector-vaccine-roundup-feb-5-sputnik-and-more

Protein glycosylation is essential for SARS-CoV-2 infection

  

View ORCID ProfileAitor Casas-Sanchez, Alessandra Romero-Ramirez, Eleanor Hargreaves, Edward I Patterson,  View ORCID ProfileGrant L Hughes, Tobias Zech,  View ORCID ProfileAlvaro Acosta-Serrano

doi: https://doi.org/10.1101/2021.02.05.429940

PDF: https://www.biorxiv.org/content/10.1101/2021.02.05.429940v1.full.pdf

Abstract

SARS-CoV-2 extensively N-glycosylates its surface spike (S) proteins. This post-translational modification is essential to modulate protein conformation and host cell invasion. Each S monomer can be modified with up to 22 N-glycans. To meet the high demand of protein glycosylation during virus replication, SARS-CoV-2 upregulates the expression of host N-glycosylation genes. Although a substantial amount of detail is known about the structure of S protein N-glycans, the role of N-glycosylation in SARS-CoV-2 infection remains largely undetermined. Here, we investigated the essentiality of the host N-glycosylation pathway and viral N-glycans for SARS-CoV-2 infection. When either monkey or human cells were preincubated with glycosylation inhibitors, including FDA-approved iminosugars, virus infection was significantly reduced. This infection phenotype was confirmed after RNAi knockdown of several glycosylation genes. In addition, enzymatic deglycosylation of whole viral particles confirmed that accessible oligosaccharides on the SARS-CoV-2 surface are essential for host cell infection. Altogether, we show evidence that the normal functioning of the host N-glycosylation machinery is essential not only for SARS-CoV-2 to infect, but also to produce new functional virions. These findings open the door for developing new approaches targeting N-glycosylation against COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

https://www.biorxiv.org/content/10.1101/2021.02.05.429940v1

Covid-19 pandemic dynamics following deployment of broad national immunization program

 Hagai Rossman, Smadar Shilo, Tomer Meir, Malka Gorfine*, Uri Shalit*, Eran Segal*

Abstract 

Studies on the real-life impact of the BNT162b2 vaccine, recently authorized for the prevention of coronavirus disease 2019 (COVID-19), are urgently needed. Here, we analysed the temporal dynamics of the number of new COVID-19 cases and hospitalization in Israel following a vaccination campaign initiated on December 20th, 2020. We conducted a retrospective analysis of real-world data from March 2020 to February 2021, originated from the Israeli Ministry of Health (MOH). In order to distill the effect of the vaccinations from other factors, including a third lockdown imposed in Israel on January 2021, we compared the time-dependent changes in number of COVID-19 cases and hospitalizations between (1) individuals above 60 years old eligible to receive the vaccine earlier and younger individuals (0-59 years old) and (2) cities who vaccinated early compared to late-vaccinated cities. and (3) the current lockdown versus the previous lockdown, imposed on September 2020. By February 2nd 2021, 42.8% and 27.6% of the entire Israeli population (88.9% and 77.7% of individuals older than 60 years old) received the first dose or both doses of the vaccine, respectively, or recovered from COVID-19. In mid-January, the number of COVID-19 cases and hospitalization started to decrease, with a larger and earlier decrease among older individuals. This trend was more evident in early-vaccinated compared to late-vaccinated cities. Such a pattern was not observed in the previous lockdown. Our analysis demonstrates early signs for the real-life effectiveness of a national vaccination campaign in Israel on the pandemic dynamics. Although our findings are preliminary, we decided to publish them as they have major public health implications in the struggle against the COVID-19 pandemic. More studies aimed at assessing the effectiveness of vaccination both on the individual and on the population level, with larger followup are needed.

https://github.com/hrossman/Patterns-of-covid-19-pandemic-dynamics-following-deployment-of-a-broad-national-immunization-program/raw/main/2021-02-03%20%20-%20Patterns%20of%20covid-19%20pandemic%20dynamics%20following%20deployment%20of%20a%20broad%20national%20immunization%20program.pdf

A Private Fix for Public Health

 Just before the first cases of the novel coronavirus began popping up in the U.S. around this time last year, public-health agencies’ biggest concern seemed to be e-cigarettes.

In January 2020, the Food and Drug Administration announced stringent bans on many of these nicotine-vapor products, teenagers’ use of which former FDA director Scott Gottlieb called an “epidemic.” That same month, the Centers for Disease Control ended its months-long recommendation that all Americans avoid e-cigarettes, after mistakenly blaming them for causing several thousand cases of lung injury nationwide. Other CDC initiatives in 2019 had included examining what foods should be sold at highway rest stops, encouraging urban planners to build more walking-friendly cities, and trying to influence how Hollywood portrays epidemics.

For all this activity, though, the CDC was failing in its core public-health functions. Despite an $11 billion budget, the agency had never produced useful modeling of how a novel virus might spread and be contained. In March 2020, Anthony Fauci, the nation’s top public-health official, was telling Americans not to wear masks. CDC arrogance and bureaucracy led to contaminated and delayed testing. A recent Reuters investigative report highlights how the agency missed early opportunities to identify asymptomatic spread of Covid-19.

The restrictions that public-health officials have put on American public life have been ad hoc and ineffective. How are liquor stores essential, but not schools? Despite imposing some of the nation’s strictest Covid lockdowns, California has a 45 percent higher hospitalization rate than Florida, which has remained relatively open.

When President Trump promised that a Covid vaccine would be developed within months, the nation’s top public-health experts scoffed. “At the earliest, a year to a year and a half, no matter how fast you go,” said Fauci last March. Private pharmaceutical companies proved the naysayers wrong—but then public-health officials botched the vaccine rollout, contributing to even more suffering and death.

U.S. public health must return to its core function of protecting Americans from transmissible diseases—not from themselves. A downsized CDC should rebrand under its original name, the Communicable Disease Center, and stop trying to control behavioral health decisions like vaping.

Bureaucracies always resist reform, but philanthropy can play a role here, funding innovative private alternatives to public health. Ample historical precedent exists for such an effort. Philanthropy played a role in building the nation’s public-health infrastructure. A local businessman’s idea and generosity led to the founding in 1912 of Tulane’s School of Hygiene and Tropical Medicine, the first institution of its kind. The Rockefeller Foundation founded the nation’s second, the Johns Hopkins School of Hygiene, once known as the “West Point of Public Health.” The Milbank Memorial Fund helped model municipal health departments, including Syracuse’s. Before these foundations existed, wealthy individuals built public baths, clinics, and dispensaries in impoverished neighborhoods of major cities.

Philanthropists can once again lead the way in remodeling our public-health institutions. The effort might start with a nonpartisan citizens’ committee to engage in a military-style “after-action” analysis of the pandemic response to identify shortcomings and fixes. Such a report might identify problems like the CDC’s monopolization of testing and lack of early contact tracing as targets for future philanthropic efforts.

A new infectious-disease school—devoted to science rather than fashionable political causes—could also catalyze a renaissance in the theory and practice of public health. More ambitious philanthropy could support private alternatives to the CDC or even to the feckless World Health Organization.

We can’t control when the next pandemic will strike, but we can vastly improve our response by empowering private institutions to bolster, if not surpass, our sclerotic public-health bureaucracy.

Carl Schramm is University Professor at Syracuse University. He was CEO of the Kauffman Foundation from 2002 to 2012. His most recent book is Burn the Business Plan.

https://www.city-journal.org/how-private-philanthropy-can-fix-public-health

New AI tool can thwart coronavirus mutations

 USC researchers have developed a new method to counter emergent mutations of the coronavirus and hasten vaccine development to stop the pathogen responsible for killing thousands of people and ruining the economy.

Using artificial intelligence (AI), the research team at the USC Viterbi School of Engineering developed a method to speed the analysis of vaccines and zero in on the best potential preventive medical therapy.

The method is easily adaptable to analyze potential mutations of the virus, ensuring the best possible vaccines are quickly identified—solutions that give humans a big advantage over the evolving contagion. Their machine-learning model can accomplish vaccine design cycles that once took months or years in a matter of seconds and minutes, the study says.

"This AI framework, applied to the specifics of this virus, can provide vaccine candidates within seconds and move them to clinical trials quickly to achieve preventive medical therapies without compromising safety," said Paul Bogdan, associate professor of electrical and computer engineering at USC Viterbi and corresponding author of the study. "Moreover, this can be adapted to help us stay ahead of the coronavirus as it mutates around the world."

The findings appear today in Nature Research's Scientific Reports

When applied to SARS-CoV-2—the virus that causes COVID-19—the computer model quickly eliminated 95% of the compounds that could've possibly treated the pathogen and pinpointed the best options, the study says.

The AI-assisted method predicted 26 potential vaccines that would work against the coronavirus. From those, the scientists identified the best 11 from which to construct a multi-epitope vaccine, which can attack the spike proteins that the coronavirus uses to bind and penetrate a host cell. Vaccines target the region—or epitope—of the contagion to disrupt the spike protein, neutralizing the ability of the virus to replicate.

Moreover, the engineers can construct a new multi-epitope vaccine for a new virus in less than a minute and validate its quality within an hour. By contrast, current processes to control the virus require growing the pathogen in the lab, deactivating it and injecting the virus that caused a disease. The process is time-consuming and takes more than one year; meanwhile, the disease spreads.

USC method could help counter COVID-19 mutations

The method is especially useful during this stage of the pandemic as the coronavirus begins to mutate in populations around the world. Some scientists are concerned that the mutations may minimize the effectiveness of vaccines by Pfizer and Moderna, which are now being distributed. Recent variants of the virus that have emerged in the United Kingdom, South Africa and Brazil seem to spread more easily, which scientists say will rapidly lead to many more cases, deaths and hospitalizations.

But Bogdan said that if SARS-CoV-2 becomes uncontrollable by current vaccines, or if new vaccines are needed to deal with other emerging viruses, then USC's AI-assisted method can be used to design other preventive mechanisms quickly.

For example, the study explains that the USC scientists used only one B-cell epitope and one T-cell epitope, whereas applying a bigger dataset and more possible combinations can develop a more comprehensive and quicker vaccine design tool. The study estimates the method can perform accurate predictions with over 700,000 different proteins in the dataset.

"The proposed vaccine design framework can tackle the three most frequently observed mutations and be extended to deal with other potentially unknown mutations," Bogdan said.

The raw data for the research comes from a giant bioinformatics database called the Immune Epitope Database (IEDB) in which scientists around the world have been compiling data about the coronavirus, among other diseases. IEDB contains over 600,000 known epitopes from some 3,600 different species, along with the Virus Pathogen Resource, a complementary repository of information about pathogenic viruses. The genome and spike protein sequence of SARS-CoV-2 comes from the National Center for Biotechnical Information.

COVID-19 has led to 87 million cases and more than 1.88 million deaths worldwide, including more than 400,000 fatalities in the United States. It has devastated the social, financial and political fabric of many countries.

The study authors are Bogdan, Zikun Yang and Shahin Nazarian of the Ming Hsieh Department of Electrical and Computer Engineering at USC Viterbi.

https://medicalxpress.com/news/2021-02-ai-tool-thwart-coronavirus-mutations.html