Antibody Correlates of Protection for mRNA Vaccine

Identifying correlates of protection, or biological markers that correlate with a certain level of protection from disease helps public health experts assess vaccination performance. Picture of a COVID-19 vaccine vial.

In the rapidly shifting context of a pandemic, public health officials need a way to quickly assess how vaccinations perform in changing situations. One approach is to identify correlates of protection, or biological markers that correlate with a certain level of protection from disease. This tool is used to assess the design and formulation of annual influenza vaccines, as immune system markers that correlate with protection from flu can give developers a sense of how effective the vaccine might be for different population groups. Though they are not a replacement for rigorous clinical trials, correlates of protection can provide meaningful and predictive data for vaccine developers with smaller trial sizes and less time.

A study published in November 2021 indicated that levels of binding antibodies and neutralizing antibodies for the SARS-CoV-2 virus in blood serum are correlates of protection for Moderna, Inc.’s COVE phase 3 clinical trial of their mRNA COVID-19 vaccine.

Continue reading “Antibody Correlates of Protection for mRNA Vaccine”

Can We Prevent the Next Pandemic?

Before the respiratory virus SARS-CoV-2 ever emerged, Tom Friedrich was already studying how viruses evolve to cause pandemics. His PhD training focused on how HIV adapts to escape detection by the immune system. Since opening his lab at the University of Wisconsin—Madison in 2008, he’s studied how viruses like influenza and Zika overcome evolutionary barriers to spread and cause disease. For nearly two years, he’s been analyzing viral sequencing data generated from positive COVID-19 test samples around the state of Wisconsin.

Thomas Friedrich, professor of pathobiological sciences in the School of Veterinary Medicine. Photo by Jeff Miller / UW-Madison, provided by Thomas Friedrich.

As the COVID-19 pandemic persists, Tom continues to make important contributions to both SARS-CoV-2 research and the relevant public health response. However, his experiences have led him to ask an even bigger question: How can we prepare for the next pandemic while still battling the current one?

“What has characterized our responses to these types of disease outbreaks in the past is sort of a boom and bust cycle,” Tom says. “We spin up a massive response that often tends to get going just as the thing itself is petering out. Then interest and funding wane so that we’re not really left with any sustainable infrastructure. But with Ebola, Zika and now COVID-19 in a pretty rapid cadence, I think people are finally getting the idea that we need to have a more sustainable infrastructure that is not totally specific to the particular disease that’s causing this outbreak today.”

Continue reading “Can We Prevent the Next Pandemic?”

COVID-19 Antiviral Therapies: What Are the New Drugs, and How Do They Work?

We’re entering the third year of the global COVID-19 pandemic, and it’s far from over. There has been considerable progress with SARS-CoV-2 vaccine development, with most of the focus on mRNA vaccines and adenoviral vector vaccines. Meanwhile, novel vaccine delivery systems are being tested among efforts to develop a “pan-coronavirus” vaccine that is effective against multiple variants. One such example is ferritin nanoparticle technology developed by researchers at the Walter Reed Army Institute of Research and their collaborators. Encouraging results from nonhuman primate studies, using several SARS-CoV-2 antigens, were published in 2021 (1–3).

New COVID-19 antiviral therapies offer promise, but further data are needed before they become widely available.

The current surge in COVID-19 cases that began last month is largely due to the Omicron variant in the US, according to data from the US Centers for Disease Control and Prevention (CDC). At present, we still don’t know enough about this variant, but it’s clear that its rapid spread is forcing us to re-examine what we know about SARS-CoV-2 (4). As the virus continues to mutate, new variants will continue to emerge and spread. Although current vaccines can provide protection against multiple variants, breakthrough infections are a concern. Vaccination is still the best option to reduce the risk of infection, hospitalization, and death compared to unvaccinated people.

It’s clear that vaccines are only part of an effective response to fighting the pandemic. Along with continued vaccine development efforts, attention must also be given to antiviral drug development for people already infected with COVID-19. Due to the lengthy process for new drug development, early efforts focused on repurposing existing drugs.

Continue reading “COVID-19 Antiviral Therapies: What Are the New Drugs, and How Do They Work?”

COVID-19 Intranasal Vaccines Revisited: Can They Reduce Breakthrough Infections?

COVID-19 cases are now being identified primarily among unvaccinated individuals, according to data from the US Centers for Disease Control and Prevention (CDC). However, there has been increasing concern about so-called breakthrough infections among fully vaccinated individuals, particularly after the emergence of the SARS-CoV-2 Delta variant.

COVID-19, sars-cov-2

What is a breakthrough infection? The CDC defines it as “the infection of a fully vaccinated person.” The key finding remains that people with breakthrough infections are still far less likely to experience severe COVID-19 symptoms, in contrast with unvaccinated people; hence the importance of vaccination.

Continue reading “COVID-19 Intranasal Vaccines Revisited: Can They Reduce Breakthrough Infections?”

Virus-Like Particles: All the Bark, None of the Bite

Globally, there have been over 5 million deaths attributed to COVID-19 since the start of the pandemic. Throughout the ongoing battle against SARS-CoV-2, researchers have been studying the viral lineage and the variants that are emerging as the virus evolves over time. The more opportunities that the virus has to replicate (i.e., the more people it infects), the greater the likelihood that a new variant will emerge.

This short video from the World Health Organization explains how viral variants develop.

The US Centers for Disease Control and Prevention (CDC) classify SARS-CoV-2 variants into four groups: Variants Being Monitored (VBM), Variants of Interest (VOI), Variants of Concern (VOC) and Variants of High Consequence (VOHC). So far, no variants in the US have been identified as VOHC or VOI. Currently, the most common variant in the US is the Delta variant (which includes the B.1.617.2 and AY viral lineages), and it is classified as a VOC.

The Delta variant originated in India and spread rapidly across the UK before making its way into the US (1). Current vaccines, including mRNA and adenoviral vector vaccines, have demonstrated effectiveness against the Delta variant. However, it is a VOC because it is more than twice as contagious as previous variants, and some studies have shown that it is associated with more severe symptoms.

A recent study (2) provides one explanation for the higher infectivity of the Delta variant, using an approach based on virus-like particles (VLPs). The research team was led by Dr. Jennifer Doudna, 2020 Nobel Prize winner for her work on CRISPR-Cas9 gene editing, and Dr. Melanie Ott, director of the Gladstone Institute of Virology at the University of California–Berkeley.

Continue reading “Virus-Like Particles: All the Bark, None of the Bite”

New Assay to Study SARS-CoV-2 Interaction with Human ACE2 Receptor

Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-associated coronavirus. The most recent version, SARS-CoV-2 was first detected in China in the winter of 2019 and is responsible for the current COVID-19 (coronavirus disease 2019) global pandemic. This virus and its variants have resulted in over 200 million infections and more than 4 million fatalities world-wide. To combat this deadly outbreak the global research community has responded with remarkable swiftness with the development of several vaccines and drug therapies, all produced in record time. In addition to vaccines and drug therapies, diagnostic kits and research reagents continue to roll out to track infections and to help find additional therapies.

This peer-reviewed paper published in Nature Scientific Reports by Alves and colleagues demonstrates how a new assay can be used to discover novel inhibitors that block the binding of SARS-CoV-2 to the human ACE2 receptor as well as study how mutations in the SARS-CoV-2 Spike protein alter its apparent affinity towards human ACE2. The paper also details studies where the assay is used to detect the presence of neutralizing antibodies from both COVID-19 positive samples as well as samples from vaccinated individuals.

Continue reading “New Assay to Study SARS-CoV-2 Interaction with Human ACE2 Receptor”

What You Should Know About The Delta Variant

The Delta Variant poses a unique challenge to global health. We’ve compiled answers to some of the most common questions about Delta and other SARS-CoV-2 variants.

What is a variant?

A variant is a form of a virus that is genetically distinct from the original form.

“All organisms have mutation rates,” says Luis A Haddock, a graduate student at University of Wisconsin – Madison. “Unfortunately for us, viruses have one of the highest mutation rates of everything that currently exists. And even more unfortunately, RNA viruses have the highest mutation rates even among viruses.”

Luis works in the Friedrich Lab at UW-Madison, which has been sequencing SARS-CoV-2 genomes from positive test samples since the beginning of the pandemic. SARS-CoV-2 is constantly evolving, and sequencing can help us follow it through time and space. Most of the variants don’t behave any differently. A single nucleotide substitution might not even change the amino acid sequence of an encoded protein. However, occasionally a mutation will alter the structure or function of a protein.

Learn more about SARS-CoV-2 sequencing in the article “From Primate Models to SARS-CoV-2 Sequencing and Testing,” featuring David and Shelby O’Connor, two collaborators of the Friedrich Lab.

What is a Variant of Concern?

Continue reading “What You Should Know About The Delta Variant”

Two COVID-19 Waves in Brazil Driven by Separate Lineages of SARS-CoV-2

The Brazilian state of Amazonas experienced two distinct waves of COVID-19 infections in 2020. After the first wave, a team from the University of Sao Paolo projected that the city of Manaus would reach the theoretical threshold for herd immunity by the end of the summer. However, a second COVID-19 wave erupted in December 2020, coinciding with the rise of Variant of Concern (VOC) P.1.

3d model of coronavirus covid-19

New research published in Nature Medicine examined the different lineages of COVID-19 present in Brazil over time and determined that the two waves were driven by different variants. The first wave was driven by the variant B.1.195, which was imported from Europe in the spring. The second wave was largely driven by VOC P.1. The Nature Medicine study is the first to use viral sequences from samples collected throughout 2020 to explore the epidemiological and virological factors behind the two distinct COVID-19 waves.

Detecting VOC P.1 in Amazonas Samples

The researchers started by generating whole-genome sequences of 250 SARS-CoV-2 samples collected between March 2020 and January 2021. The survey showed that 20% of the sequences belonged to the B.1.195 lineage, and these mostly corresponded with the first exponential growth phase. 24% of the samples belonged to the P.1 lineage, and all of these samples corresponded with the rise of the second exponential growth phase. The largest share belonged to B.1.1.28 (37%), which replaced B.1.195 as the dominant variant in Brazil shortly after the first wave until the rise of VOC P.1.

The team also used real-time RT-PCR to analyze 1,232 positive samples collected in Amazonas between November 1, 2020 and January 21, 2021. The assay was designed to detect a deletion in NSP6, which is a signature mutation of VOC P.1. None of the samples collected before December 16 showed the NSP6 deletion, but it was common in samples starting in mid-December. Combining the two analysis methods, the team found the P.1 lineage in 0% of samples collected in November 2020, but by January 1-15 it was present in 73.8% of samples.

This data supports the theory that VOC P.1 first emerged in December 2020 and was the dominant lineage driving the second wave in Amazonas.

Two COVID-19 Waves: Virological and Epidemiological Factors

In addition to tracking the prevalence of lineages throughout the pandemic, the researchers also offered suggestions for how Amazonas experienced two distinct waves of COVID-19 infections.

Using computer modeling, the team found a significant reduction in reproductive efficiency (Re) of lineages B.1.195 and B.1.1.28 in April-May 2020, around the same time that Amazonas increased social distancing measures. Transmission rates remained low until the interventions were relaxed in September 2020. This suggests that the reduction in cases was not a result of herd immunity. Instead, nonpharmaceutical interventions (NPI) limited the first wave and contained the spread through the summer.

Using real-time RT-PCR, the researchers found that the viral load of P.1 infections was nearly ten times the viral load of non-P.1 infection. They also referenced other research that found that VOC P.1 has a stronger affinity for the human receptor ACE2 than B.1.195 and B.1.1.28. P.1 is clearly a highly transmissible VOC, and it evolved in an ideal environment for rapid spread. Amazonas had relaxed social distancing measures by late 2020, P.1 was able to quickly reach extremely high infection rates.

The study did not directly address theories that P.1 evades immunity developed from prior infections, but they concluded that a combination of epidemiological and virological factors allowed P.1 to drive a second wave of COVID-19 in Amazonas starting in December.

The paper includes a supplementary note suggesting that NPIs instituted in Manaus in January 2021 significantly reduced transmission rates of VOC P.1. The team ends the paper by reiterating the importance of adequate social distancing measures to limit the spread of COVID-19 and prevent the emergence of new Variants of Concern.

Read the entire paper here.


This study used the Maxwell® RSC Viral Total Nucleic Acid Purification Kit to extract viral RNA from samples. Learn more about the kit and its uses during the COVID-19 pandemic here.


Understanding Inflammation: A Faster, Easier Way to Detect Cytokines in Cells

Inflammation, a process that was meant to defend our body from infection, has been found to contribute to a wide range of diseases, such as chronic inflammation, neurodegenerative disorders—and more recently, COVID-19. The development of new tools and methods to measure inflammation is crucial to help researchers understand these diseases.

This diagram shows how the Lumit™ Immuno assay can be used to detect cytokines.

Cytokines—small signaling molecules that regulate inflammation and immunity—have recently become the focus of inflammation research due to their role in causing severe COVID-19 symptoms. In these severe cases, the patient’s immune system responds to the infection with uncontrolled cytokine release and immune cell activation, called the “cytokine storm”. Although the cytokine storm can be treated using established drugs, more research is needed to understand what causes this severe immune response and why only some patients develop it.

Continue reading “Understanding Inflammation: A Faster, Easier Way to Detect Cytokines in Cells”

What Is A Viral Variant?

Every time a genome is replicated, there’s a chance that an error will be introduced. This is true for all life forms. On a small scale, these mutations can lead to genetic diseases or cancers. On a much larger scale, random mutations are an important tool of evolution.

During the COVID-19 pandemic, the SARS-CoV-2 virus has picked up many mutations as it spread around the world. Most of these mutations have been inconsequential – the virus didn’t change in any significant way. Others have given rise to variants such as B.1.1.7 and B.1.351, which present complications for public health efforts. By studying the evolution of the virus, we can monitor how it’s spreading and predict the characteristics of variants as they are detected.

SARS-CoV-2 variant
David Goodsell Painting of SARS-CoV-2 Virus
Continue reading “What Is A Viral Variant?”