COVID-19 Intranasal Vaccines: Right on the Nose?

covid-19 intranasal vaccines

COVID-19 is still a global pandemic. Around the world, as of 5:40pm CEST, 20 June 2022, there have been 536,590,224 cumulative confirmed cases of COVID-19, including 6,316,655 deaths, reported to the World Health Organization. As of 16 June 2022, a total of 11,902,271,619 vaccine doses have been administered. The adoption of vaccines worldwide continues to increase, yet periodic spikes and surges in infection rates continue to occur with new SARS-CoV-2 variants, such as that observed in Australia over the past few months. Vaccine booster doses provide effective protection against developing severe disease and hospitalization, but vaccine adoption and distribution face ongoing challenges in low- and middle-income (LMIC) countries (1). Therapeutic interventions for those already infected are in development, with one (Paxlovid) currently available under emergency use authorization (EUA) in the US.

COVID-19 cumulative statistics reported to the WHO.

Cumulative COVID-19 statistics by country: WHO COVID-19 Dashboard. Geneva: World Health Organization, 2020. Available online: https://covid19.who.int/ (last cited: June 20, 2022).

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Detecting SARS-CoV-2 In Wastewater: The New Frontier in Pandemic Surveillance

Tracking the spread of COVID-19 has been a tremendous challenge throughout the pandemic, but doing so is a key step toward containing the virus. Many communities have relied on patient testing and contact tracing, with limited success. In search of better methods, some countries have made inroads in a different form of disease surveillance: wastewater-based epidemiology (WBE). This approach involves testing wastewater for the presence of pathogens, primarily through DNA and RNA analysis, and has proved to be an accurate and highly effective way to keep tabs on the prevalence and progression of COVID-19 at the population level.

Switzerland is among those countries that have implemented WBE in their efforts to stay ahead of the pandemic. Since WBE first emerged in 2020 as a promising tool, several Swiss laboratories undertook wastewater testing, and protocols were established early.

“At the beginning, the methods to actually detect coronavirus in wastewater were rather laborious and complicated, and involved a lot of resources,” said Dr. Claudia Bagutti, microbiologist and molecular biologist in the State Laboratory of Basel-City, Switzerland.

Bagutti heads a small team performing applied biosafety research. In 2020, her lab was tasked with developing an assay for detecting COVID-19 in wastewater. However, the available methods were prohibitively complex and resource intensive.

In the meantime, researchers at Promega recognized that Promega products and methodologies could potentially be applied to WBE and set to work developing simpler and more efficient method for wastewater analysis. In the spring of 2021, Bagutti’s team decided to try adopting this method.

“Promega had a very nice method which was less laborious and much easier to handle, and that’s why we gave it a try,” said Bagutti.

In the ensuing study, Bagutti and her team analyzed effluent from the catchment area of one municipal wastewater plant in Switzerland. They examined the total wastewater output of around 270,000 people. Viral RNA was extracted using Promega’s Maxwell® RSC Environ Wastewater TNA Kit. The number of RNA copies present, representing the overall concentration of COVID-19 in each sample, was determined via quantitative reverse transcriptase (RT-qPCR) using the GoTaq® Enviro Wastewater SARS-CoV-2 Systems, also from Promega. The viral RNA was subsequently sequenced with next generation sequencing, and the results correlated quite well with the COVID-19 cases in the catchment area. Remarkably, this study detected the Omicron variant in a wastewater sample one day prior to the first reported case identified through patient testing.

“We observed a similar spread to most other western countries with respect to the time of the first discovery of these variants,” said Bagutti. “We were also able to demonstrate the presence [of Omicron] in the wastewater before it came up in a sample of a COVID-19 patient test, which of course shows the usefulness of wastewater monitoring for the prediction of new variants and infection dynamics.”

WBE is especially promising in that it provides population-level data independent of patient testing. Health departments can be alerted to the presence of COVID-19 earlier than would otherwise be possible with traditional testing and can take precautions to contain the spread. In creating a more user-friendly method for wastewater analysis, Promega has opened the door for more laboratories to conduct WBE, which could provide communities around the world with the information they need to preempt the progression of COVID-19.

“The Promega method is very straightforward to handle,” said Bagutti. “It only takes a small volume of wastewater, which makes it handy. It’s less time-consuming compared to the methods which were in the literature at the beginning of the pandemic, and it just works very well. We also did experience great support from Promega.”

At this point, much of the wastewater analysis performed in Switzerland is done with the Promega method, including in federal, state or private labs. The swift advance of WBE in Switzerland speaks to the colossal effort put forth both by Promega researchers in developing the necessary products and methodologies, as well by those labs that have made use of Promega’s products to monitor COVID-19 in wastewater.

“It’s really been a success story for us, from the beginning,” said Bagutti.


Learn more about Promega’s work with wastewater-based epidemiology.

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.

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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.

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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.

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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.

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Streamlining Research: The Merits of Adaptive Clinical Trials

Clinical trials are arguably the backbone of medical advancement. But the trials most worth doing are usually large, costly and time-intensive, demanding extensive resources and personnel. During the COVID-19 pandemic, there has been a marked uptick in the number of clinical trials, many of which are woefully flawed with issues ranging from insufficient sample size to bad design. The published research that follows is often redundant or inconclusive.

So how can scientists designing and running clinical trials streamline their efforts to reduce waste and achieve more useful outcomes? The answer could be adaptive clinical trials.

Adaptive clinical trials are designed so they can be modified as data are being collected
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Seeing is Believing: How NanoLuc® Luciferase Illuminates Virus Infections

Artists interpretation of in vivo imaging of viral infections in mice using NanoLuc luciferase.

Wearing blue surgical gowns and white respirator hoods, research scientist Pradeep Uchil and post-doctoral fellow Irfan Ullah carry an anesthetized mouse to the lab’s imaging unit. Two days ago, the mouse was infected with a SARS-CoV-2 virus engineered to produce a bioluminescent protein. After an injection of a bioluminescence substrate, a blue glow starts to emanate from within the mouse’s nasal cavity and chest, visible to the imaging unit’s camera and Uchil’s eyes.

“We were never able to see this kind of signal with retrovirus infections.” Uchil is a research scientist at the Yale School of Medicine whose work focuses on the in vivo imaging of retroviral infections. Normally, the mouse would have to be sacrificed and “opened up” for viral bioluminescent signals from internal tissues to be imaged directly.

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From Drug Use to Viral Outbreaks, How Monitoring Sewage Can Save Lives

Most of us, after we flush the toilet, don’t think twice about our body waste. To us, it’s garbage. To epidemiologists, however, wastewater can provide valuable information about public health and help save lives.

History of Wastewater-Based Epidemiology

Wastewater-based epidemiology (WBE) is the analysis of wastewater to monitor public health. The term first emerged in 2001, when a study proposed the idea of analyzing wastewater in sewage-treatment facilities to determine the collective usage of illegal drugs within a community. At the time, this idea to bridge environmental and social sciences seemed radical, but there were clear advantages. Monitoring wastewater is a nonintrusive and relatively inexpensive way to obtain real-time data that accurately reflects community-wide drug usage while ensuring the anonymity of individuals.

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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?

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