Pathologists and clinical laboratory scientists know that influenza vaccines typically produce short-lived protection and researchers have new clues as to why this is true
With so much interest in development of a COVID-19 vaccine, findings by researchers at Atlanta’s Emory Vaccine Center into why the vaccine for influenza (Flu) is so short-lived offer a new window on how the body’s immune system responds to invading viruses and what happens to the immunity over time.
Because the autumn influenza season is just weeks away, these insights into the body’s immune response to influenza will be of interest to clinical laboratories that provide testing for influenza, as well as SARS-CoV-2, the coronavirus that causes COVID-19.
Clinical laboratory managers recognize that an influenza vaccine is an annual imperative for people—especially the elderly and those with existing comorbidities—and medical laboratory tests are typically used to diagnose the illness and identify which strains of viruses are present. The flu vaccine is even more important amid the COVID-19 pandemic, infectious disease authorities say.
The scientists at the Emory Vaccine Center published their findings in the journal Science.
Not so with influenza vaccines. The immunity they impart generally only lasts for a single flu season and are “lost within one year,” the Emory study notes.
As Genetic Engineering and Biotechnology News (GEN) explains, the influenza genome has eight RNA segments which can change as the virus enters a cell. This antigenic shift creates new influenza strains that require updated vaccines, GEN noted.
However, the Emory researchers stated that “The fact that a small number did persist over one year raises prospects that the longevity of flu vaccines can be improved and provides key information for the development of universal vaccines against influenza.”
Bone Marrow Has Major Role in Producing New Flu Antibodies
The Emory study focused on the influenza vaccine’s role in how it affects the immune system and what needs to change to create a longer-lasting influenza vaccine. “Our results suggest that most bone marrow plasma cells (BMPC) generated by influenza vaccination in adults are short-lived. Designing strategies to enhance their persistence will be key,” the Emory researchers wrote in Science.
The scientists analyzed bone marrow from 53 healthy volunteers (age 20 to 45). An Emory news release states that bone marrow is the “home base for immune cells producing antibodies.”
Besides the bone marrow, the researchers also examined blood samples from the volunteers, all of which was collected between 2009 and 2018:
before influenza vaccination,
one month after influenza vaccination, and
one year post vaccination.
Through DNA sequencing the samples, the Emory researchers found the number of flu-specific cells increased from 0.8% to 1.9% after one month. They concluded that an annual vaccine does increase antibody-producing cells for influenza in bone marrow.
However, in follow-up visits one year after vaccination, they found that the number of cells present in the volunteers had fallen back to the starting point.
“Specific cells produced by the vaccine … produced unique antibodies that can be identified using sequencing techniques,” Carl Davis, PhD, postdoctoral fellow in the Rafi Ahmed Laboratory at Emory and first author of the paper, said in the news release, adding, “We could see that these new antibodies expanded in the bone marrow one month after vaccination and then contracted after one year.”
He continued, “On the other hand, antibodies against influenza that were in the bone marrow before the vaccine was given stayed at a constant level over one year.”
Vaccine Adjuvants Help Boost Immunity
A vaccine additive called an adjuvant could be the answer to extending the power of influenza vaccines, the Emory scientists noted.
“Just getting to the bone marrow is not enough. A plasma cell has to find a niche within the bone marrow and establish itself there and undergo gene expression and metabolism changes that promote longevity,” Rafi Ahmed, PhD, Director of the Emory Vaccine Center, said in the news release.
“It’s totally crazy (that the most commonly used influenza vaccines don’t include an adjuvant), Ahmed told Science. “I’m hoping that things will change in the influenza vaccine world, and 10 years from now, you will not be getting any nonadjuvanted vaccines.”
According to USA Today, about 20-million “essential” workers will likely be the first to receive the new COVID-19 vaccine and participate in check-in text messages with the Centers for Disease Control and Prevention (CDC) by the end of 2020.
In its COVID-19 vaccine testing, Novavax, a late-state biotechnology company, suggests that “an adjuvant is critical to its vaccine working well,” National Public Radio (NPR) reported in “The Special Sauce That Makes Some Vaccines Work.” However, vaccine developers may be reluctant to share their adjuvant research.
“Adjuvants end up being very proprietary. It’s kind of the secret sauce on how to make your protein vaccine work,” Barney Graham, MD, PhD, Deputy Director, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, told NPR.
Still, a study published in Immunopharmacology revealed potential adjuvants for the COVID-19 vaccine based on vaccine studies of other coronaviruses. While there are many adjuvants available, not all have safety track records that can be leveraged to gain clearance from regulatory bodies, the researchers pointed out. But some do.
“CpG 1018, MF59, and AS03 are already approved for human vaccine and their inclusion may expedite the vaccine development process. Further, Protollin has shown promising results in pre-clinical studies,” the authors wrote.
Clinical laboratories that provide influenza testing will want to follow these types of research studies. Findings on immunity will affect development of vaccines that medical labs provide—including for COVID-19.
‘Aerosol and Surface Stability’ study shows that the virus can remain infectious in aerosol form for hours and on surfaces for days
By now, clinical laboratory workers, microbiologists, and phlebotomists should be fully aware of the potential for transmission on surfaces of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes Coronavirus disease 2019 (COVID-19). The CDC’s latest Morbidity and Mortality Weekly Report revealed that the coronavirus “was identified on a variety of surfaces in cabins of both symptomatic and asymptomatic infected passengers up to 17 days after cabins were vacated on the Diamond Princess, but before disinfection procedures had been conducted,” the New York Post reported. That means the virus can survive on surfaces significantly longer than CDC previously believed.
But did you know a recent study published in the New England Journal of Medicine (NEJM) found that SARS-CoV-2 can also survive in the air for many hours, potentially allowing aerosolized transmission of the virus as well?
The NEJM study also showed that the stability of SARS-CoV-2 to survive on surfaces and in aerosolized form mirrors the stability of the SARS coronavirus (SARS-CoV) that caused the severe acute respiratory syndrome (SARS) outbreak of 2003.
This is critically important information for clinical laboratory professionals in open-space laboratories, phlebotomists collecting medical laboratory specimens, and frontline healthcare workers who come in direct contact with potentially infected patients. They should be aware of every potential COVID-19 transmission pathway.
Hospital infection control teams will be particularly
interested in the possibility of airborne transmission, as they often visit
infected patients and are tasked with tracking both the source of the infection
as well as individuals who may be exposed to sick patients.
The NEJM study, titled “Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1” was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), an agency of the US Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention (CDC), Princeton University, and University of California, Los Angeles. The researchers concluded that SARS-CoV-2 remains in the air “up to three hours post aerosolization.”
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They also found the virus was detectable for up to four
hours on copper and up to 24 hours on cardboard. The scientists concluded SARS-CoV-2
can remain on plastic and stainless-steel surfaces for two to three days,
though the amount of the virus on surfaces decreases over time.
“Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days,” the study states. “These findings echo those with SARS-CoV-1, in which these forms of transmission were associated with nosocomial spread and super-spreading events, and they provide information for pandemic mitigation efforts.”
But Can COVID-19 Be Caught Through Air?
However, as noted in Wired, the researchers did not clearly state that infected persons can spread COVID-19 to others in the same airspace. Some experts have pointed out that there is a difference between a virus that can exist as an aerosol—defined as a liquid or solid suspended in gas under only limited conditions—and the measles virus, for example, which the CDC estimates “can live for up two hours in an airspace where the infected person has coughed or sneezed.”
“While the researchers tested how long the virus can survive
in aerosols suspended in the air, they didn’t actually sample the air around
infected people,” Wired noted. “Instead, they put the virus into a
nebulizer and puffed it into a rotating drum to keep it airborne. Then, they
tested how long the virus could survive in the air inside the drum.”
Neeltje van Doremalen, PhD, a research fellow at National Institutes of Health (NIH) and researcher at the NIAID’s Rocky Mountain Laboratories in Hamilton, Montana, who coauthored the NEJM study, cautioned against an overreaction to this latest research. On Twitter she wrote, “Important: we experimentally generated [COVID-19] aerosols and kept them afloat in a drum. This is not evidence of aerosol transmission.”
Nonetheless, the World House Organization (WHO) took note of the study’s findings and on March 16, 2020, announced it was considering “airborne precautions” for healthcare workers, CNBC reported in its coverage of a virtual press conference on March 16, 2020, led by Maria Van Kerkhove, MS, PhD, Technical Lead for WHO’s Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Task Force.
Van Kerkhove emphasized that health officials were
monitoring results from other studies investigating how environmental
conditions such as humidity, temperature, and ultraviolet light affect
the disease and its ability to live on different surfaces.
“When you do an aerosol-generating procedure like in a medical care facility, you have the possibility to what we call aerosolize these particles, which means they can stay in the air a little bit longer,” said Maria Van Kerkhove, MS, PhD (above), Technical Lead for WHO’s Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Task Force during a virtual press conference, CNBC reported. “It’s very important that healthcare workers take additional precautions when they’re working on patients and doing these procedures,” she added. [Photo copyright: World Health Organization/YouTube.)
To Be or Not to Be an Airborne Pathogen
Stanley Perlman, MD, PhD, Professor of Microbiology and Immunology at the University of Iowa, believes aerosol transmission ultimately will be found not to play a large role in COVID-19 transmission.
“I think the answer will be, aerosolization occurs rarely, but not never,” Perlman told STAT. “You have to distinguish between what’s possible and what’s actually happening.”
In an NEJM editorial, Perlman expanded on those thoughts. “Although specific anti-coronaviral therapies are still in development, we now know much more about how to control such infections in the community and hospitals, which should alleviate some of this fear,” he wrote. “Transmission of [SARS-CoV-2] probably occurs by means of large droplets and contact and less so by means of aerosols and fomites, on the basis of our experience with SARS-CoV and MERS-CoV. Public health measures, including quarantining in the community as well as timely diagnosis and strict adherence to universal precautions in healthcare settings, were critical in controlling SARS and MERS. Institution of similar measures will be important and, it is hoped, successful in reducing the transmission of [SARS-CoV-2].”
An NIH news release announcing the SARS-CoV-2 stability study highlighted two additional observations:
“If the viability of the two coronaviruses is
similar, why is SARS-CoV-2 resulting in more cases? Emerging evidence suggest
that people infected with SARS-CoV-2 might be spreading virus without
recognizing, or prior to recognizing, symptoms. That would make disease control
measures that were effective against SARS-CoV-1 less effective against its
successor.
In contrast to SARS-CoV-1, most secondary cases
of virus transmission of SARS-CoV-2 appear to be occurring in community
settings rather than healthcare settings. However, healthcare settings are also
vulnerable to the introduction and spread of SARS-CoV-2, and the stability of
SARS-CoV-2 in aerosols and on surfaces likely contributes to transmission of
the virus in healthcare settings.”
Clearly, the scientific community has not agreed on
aerosolization as a definite source of infection. Nevertheless, clinical
laboratory workers in settings where potential exposure to SARS-CoV-2 exists
should take precautions against airborne transmission until scientists can
definitively determine whether this latest coronavirus can be acquired through
the airborne transmission.
Scientist described the speed at which SARS-CoV-2’s full sequence of genetic material was made public as ‘unprecedented’ and medical labs are rushing to validate tests for this new disease
In the United States, headlines scream about the lack of
testing for the novel Coronavirus
disease 2019 (COVID-19). News reporters ask daily why it is taking so long
for the US healthcare system to begin testing large numbers of patients for
SARS-CoV-2, the virus that causes COVID-19. Yet, pathologists
and clinical
laboratory scientists know that new technologies for gene sequencing
and diagnostic testing are helping public health laboratories bring up tests
for a previously unknown new disease faster than at any time in the past.
At the center of the effort to develop accurate new assays
to detect SARS-CoV-2 and help diagnose cases of the COVID-19 disease are medical laboratory
scientists working in public health
laboratories, in academic medical centers, and in research labs across the
United States. Their collective efforts are producing results on a faster
timeline than in any previous discovery of a new infectious disease.
For example, during the severe
acute respiratory syndrome (SARS) outbreak in 2003, five months passed
between the first recognized case of the disease in China and when a team of
Canadian scientists cracked the genetic code of the virus, which was needed to
definitively diagnose SARS patients, ABC
News reported.
In contrast, Chinese scientists sequenced this year’s
coronavirus (originally named 2019-nCoV) and made it available on Jan. 10,
2020, just weeks after public health officials in Wuhan, China, reported the
first case of pneumonia from the unknown virus to the World Health Organization
(WHO), STAT
reported.
Increases in sequencing speed enabled biotechnology
companies to quickly create synthetic copies of the virus needed for research. Roughly
two weeks later, scientists completed sequencing nearly two dozen more samples
from different patients diagnosed with COVID-19.
Molecular biologist Kristian Andersen, PhD (above right, with graduate students who helped sequence the Zika virus), an Associate Professor in the Department of Immunology and Microbiology at Scripps Research in California and Director of Infectious Disease Genomics at Scripps’ Translational Research Institute, worked on the team that sequenced the Ebola genome during the 2014 outbreak. He told STAT that the pace of sequencing of the SARS-CoV-2 coronavirus is “unprecedented.” (Photo copyright: Scripps Research.)
Lower Sequencing Costs Speed COVID-19 Diagnostics Research
Additionally, a significant decline in the cost of genetic synthesis is playing an equally important role in helping scientists slow the spread of COVID-19.In its coverage of the SARS-CoV-2 outbreak, The Verge noted that two decades ago “it cost $10 to create a synthetic copy of one single nucleotide, the building block of genetic material. Now, it’s under 10 cents.” Since the coronavirus gene is about 30,000 nucleotides long, that price reduction is significant.
Faster sequencing and cheaper access to synthetic copies is
contributing to the development of diagnostic tests for COVID-19, an important
step in slowing the disease.
“This continues to be an evolving situation and the ability to distribute this diagnostic test to qualified medical laboratories is a critical step forward in protecting the public health,” FDA Commissioner Stephen M. Hahn, MD, said in an FDA statement.
However, the Washington Post soon reported that the government-created coronavirus test kits contained a “faulty component,” which as of February 25 had limited testing in the US to only 426 people, not including passengers who returned to the US on evacuation flights. The Post noted that the nation’s public health laboratories took “the unusual step of appealing to the FDA for permission to develop and use their own [laboratory-developed] tests” for the coronavirus.
“This is an extraordinary request, but this is an extraordinary time,” Scott Becker,
Parallel efforts to develop and validate tests for COVID-19
are happening at the clinical laboratories of academic medical centers and in a
number of commercial laboratory companies. As these labs show their tests meet
FDA criteria, they become available for use by physicians and other healthcare
providers.
Dark Daily’s sister publication, The Dark Report just published an intelligence briefing about the urgent effort at the clinical laboratory of Northwell Health to develop both a manual COVID-19 assay and a test that can be run on the automated analyzers already in use in the labs at Northwell Health’s 23 hospitals. (See TDR, “Northwell Lab Team Validates COVID-19 Test on Fast Timeline,” March 9, 2020.)
Following the FDA’s March 13 EUA for the Thermo Fisher test,
Hahn said, “We have been engaging with test developers and encouraging them to
come to the FDA and work with us. Since the beginning of this outbreak, more
than 80 test developers have sought our assistance with development and
validation of tests they plan to bring through the Emergency Use Authorization
process. Additionally,” he continued, “more than 30 laboratories have notified
us they are testing or intend to begin testing soon under our new policy for
laboratory-developed tests for this emergency. The number of products in the
pipeline reflects the significant role diagnostics play in this outbreak and
the large number of organizations we are working with to bring tests to
market.”
Pharma Company Uses Sequencing Data to Develop Vaccine in
Record Time
Even as clinical laboratories work to develop and validate diagnostic tests for COVID-19, drug manufacturers are moving rapidly to develop a COVID-19 vaccine. In February, Massachusetts-based biotechnology company Moderna Therapeutics (NASDAQ:MRNA) announced it had shipped the first vials of its potential coronavirus vaccine (mRNA-1273) to the National Institute of Allergy and Infectious Disease (NIAID) for use in a Phase One clinical trial.
“The collaboration across Moderna, with NIAID, and with CEPI [Coalition for Epidemic Preparedness Innovations] has allowed us to deliver a clinical batch in 42 days from sequence identification,” Juan Andres, Chief Technical Operations and Quality Officer at Moderna, stated in a news release.
The Wall Street Journal (WSJ) reported that NIAID expects to start a clinical trial of about 20 to 25 healthy volunteers by the end of April, with results available as early as July or August.
“Going into a Phase One trial within three months of getting the sequence is unquestionably the world indoor record,” NIAID Director Anthony Fauci, MD, told the WSJ. “Nothing has ever gone that fast.”
There are no guarantees that Moderna’s coronavirus vaccine
will work. Furthermore, it will require further studies and regulatory
clearances that could delay widespread distribution until next year.
Nonetheless, Fauci told the WSJ, “The only way you
can completely suppress an emerging infectious disease is with a vaccine. If
you want to really get it quickly, you’re using technologies that are not as
time-honored as the standard, what I call antiquated, way of doing it.”
In many ways, the news media has overlooked all the important
differences in how fast useful diagnostic and therapeutic solutions for
COVID-19 are moving from research settings into clinical use, when compared to
early episodes of the emergence of a new infectious disease, such as SARS in
2003.
The story the American public has yet to learn is how new
genetic sequencing technologies, improved diagnostic methods, and enhanced
informatics capabilities are being used by researchers, pathologists, and
clinical laboratory professionals to understand this new disease and give
healthcare professionals the tools they need to diagnose, treat, and monitor
patients with COVID-19.
Lab-on-a-chip technology could reduce the time needed to identify infection-causing bacteria and for physicians to prescribe correct antibiotics
Pathology groups and medical laboratories may see their role in the patient-care process grow if researchers succeed in developing culture-independent diagnostic tools that quickly identify bacterial infections as well as pinpoint the antibiotics needed to treat them.
In the battle against antibiotic-resistant infections (AKA “super bugs”) the National Institutes of Health (NIH) is funding nine research projects aimed at thwarting the growing problem of life-threatening infections that no longer are controlled or killed by today’s arsenal of drugs.
Common Practices in Hospitals Leading to Super Bugs
Currently, when infections are suspected in hospitals or other settings where illness can quickly spread, samples are sent to a central medical laboratory where it may take up to three days to determine what germ is causing the infection. Because of that delay, physicians often prescribe broad-spectrum antibiotics based on a patient’s symptoms rather than lab test results, a practice that can lead to the growth of antibiotic-resistant microbes. (more…)
