America’s Vaccine-Centric Strategy to Overcome SARS-CoV-2 Failing While Adequate Universal Testing & Data Collection ‘Grossly Inadequate’
One of the most influential physicians and researchers in America declared recently that a “vaccine-centric” strategy has precluded important other strategies in the war against COVID-19, such as pervasive, ubiquitous testing as well as relevant data collection. They don’t get much smarter or revered than Dr. Eric Topol, an outspoken, honest—and brilliant—founder of the Scripps Research Translational Institute. Nominated as one of America’s most influential physician leaders by Modern Healthcare, Dr. Topol has published over 1,200 entries in peer review journals, authored three best-selling books, and frequently communicated on the challenges of COVID-19. With a large and loyal following, Topol’s known for his reputation for objectivity and candor, making him a favorite of scientists who appreciate his independence. Considered trustworthy in a special influence-driven age, Topol’s recent critical assessment of the most recent delta variant-driven surge suggests, “America is flying in the blind when it comes to the delta variant.” The lack of pervasive testing and proper data collection makes the pandemic far worse for America, suggests Topol. With growing virulent, highly transmissible SARS-CoV-2 strains such as delta, America’s “vaccine-centric’ strategy cannot get us out of this pandemic, not alone, articulates Topol. The lack of testing and a dearth of mission-critical testing makes the pandemic worse, less containable, and thus our future, at least in the short run, more uncertain. From the Centers for Disease Control and Prevention (CDC) on down, America’s health systems have depended too much on vaccines. The strategy may have worked, but not for delta. Now the doctor argues we need to mobilize testing and more holistic data collection, and fast. Also key to stopping SARS-CoV-2 transmission, argues Topol, is the concept of mucosal immunity—intranasal vaccines can potentially deliver this or vaccines targeting the upper respiratory areas—the zone where SARS-CoV-2 enters and thrives. But the National Institutes of Health and the pharmaceutical industry focused on blood-based immunity; they use the bloodstream to induce igG antibodies to various parts of the virus. But this current crop of vaccines, despite tens of billions spent, doesn’t include long-lasting immunoglobulin A, argues Topol, the type of antibody we need in our nose and upper airway.
Kyle Allred is the co-founder of MedCram, an important website providing medical videos and lectures explained clearly. He recently interviewed Dr. Topol, who provided a candid assessment of the unfolding delta variant-driven COVID-19 surge.
‘Flying Blind’
Topol recently published a piece titled “America is flying blind when it comes to the delta variant” in The Guardian. The influential doctors emphasize that the lack of data involving breakthrough infections spells real trouble, giving Americans a “false sense of security.” He points to the CDC as falling well short of expectation. But why?
America’s Health Leaders Failing
Topol emphasizes that this particular surge is the absolute most difficult challenge of the pandemic to date. America is “flying blind” because the nation’s health care systems, such as the CDC, are not effectively tracking the relevant data, leaving the country flatfooted for any imminent pivots that could lead to better outcomes. With over 70,000 people in the hospital, America has no idea who was vaccinated, when they were vaccinated, their age, co-existing conditions, and so much more.
Frankly, it’s truly shocking when internalizing his true message. Given the amount of money spent on vaccines and pharmaceutical therapies alone, not to mention the billions to get people in for a jab, Topol emphasizes that much of the data we need now for a real analysis just isn’t there. Topol argues this is the absolute basis for understanding the pandemic’s wrath, especially in hot spots such as Florida.
Dearth of Testing in America
Compared to other developed national testing schemes, America to date, in this pandemic is pretty much an abject failure. Comparing the American effort to track and collect data, such as frequent testing, as compared to other developed nations, from the U.K. to Israel and nations in Europe, Topol declared, “we have a problem because we are not testing.” America tests at about one-fifth of the systematic testing as seen in the U.K. and Israel. Calling the American effort “grossly inadequate,” Topol declared, “we don’t really have a good handle on the denominator of cases out there.”
Thus, a dysfunctional confluence of three deficiencies makes it impossible for healthcare analysts to truly understand the situation at the local state or national level. A lack of 1) trust, 2) testing, and 3) rapid home-testing equates to no real handle on infectiousness and the lack of critical data elements that could lead to better pandemic controls.
Without testing combined with a rudimentary data collection, Topol declares that, in all reality, American health leadership doesn’t even really know if vaccines are working. Or how extensive they may work—or for that matter, how to achieve “best practices” to help control and contain the virus as soon as possible. Of course, Topol praises the vaccines in that they have worked better than expected, but blind faith in that approach missed the left hook of delta and the basic need for more comprehensive data. These can lead to a knockout blow.
Failure of ‘Vaccine-centric Strategy”
Why hasn’t America adopted rapid testing? Topol shared that he and Harvard’s School of Public Health Michael Mina, a big universal testing advocate, are “united’ on the topic. He shared that many advanced countries are deploying these rapid tests to better control and contain the virus, providing free tests for schools—for teachers, students, bus drivers, and the like.
For example, Germany and others are going through the delta-based surge, but with much less hospitalization per capita in part because they have more comprehensive and holistic public health measures involving data, that is, obsessive testing for starters. The New York Times published a piece on the subject titled “Germany makes rapid tests a key to everyday freedoms.”
But Topol gets down to the real reason America hasn’t embraced testing: that is, the nation is overly dependent on a “vaccine-centric strategy” that Topol suggests “would have worked, “but then came “delta.”
Topol shares that the current vaccination cannot sterilize the environment to rid the world of SARS-CoV-2. He declares that the vaccines were amazing, but they were never perfect, nor were they designed “to achieve sterilization mucosal immunity.” Topol emphasizes that it would require an “intranasal vaccine,” and that kind of vaccine was never emphasized by the National Institutes of Health (NIH) or Operation Warp Speed and the U.S. Department of Health and Human Services (HHS), Biomedical Advanced Research Development Authority (BARDA). After all, tens of billions of taxpayer-originated dollars went to subsidizing vaccine and monoclonal antibody development. The government knew early on that SARS-CoV-2 was an upper respiratory viral infection, so why wouldn’t government funders have sought to diversify the vaccine portfolio?
Why is an Intranasal Vaccine Critical Moving Forward?
The current first crop of COVID-19 vaccines are blood-based, in that they use the bloodstream to trigger igG antibodies to various parts of the virus, such as proteins. However, the current vaccines don’t produce “long-lasting immunoglobulin A, the type of antibody we need in our nose and upper airway,” shares Topol with Medcram’s Allred. The current vaccines are based on a “blood-specific strategy” and don’t sufficiently elicit defenses in the upper airways, where SARS-CoV-2 enters and thrives. With a nasal vaccine, a more potent defense against the virus is possible via “mucosal immunity.”
Perhaps if the existing type of vaccine had been combined with an effective intranasal vaccine, the adoption would probably be far greater (people prefer a nasal spray to a large injection or two) and the chances of overcoming even the delta variant would be much better.
The current vaccine products don’t factor in the area of most risk, our nose and upper airway, where we, according to Topol, “leak.”
Topol notes that the current vaccines contribute T cells and killer T cells that help trigger immunity, which explains why the vaccinated don’t end up hospitalized nearly as much as the unvaccinated. But to actually stop the spread of this pathogen would require, according to Topol, mucosal immunity.
What about a Third Dose or Booster?
Topol rightly raises profound issues, such as health equity, pointing out that much of the world’s low-and middle-income country (LMICs) has very low vaccination rates coupled with surging delta-driven pandemics. He ponders what will happen in a connected world where the rich are vaccinated, and the poor go without.
He also considers the direction unfolding, with growing breakthrough infections and the waning effectiveness of vaccines, and the likelihood of the need for a booster being high. He acknowledged that he hasn’t been too keen on this prospect, especially if Pfizer and Moderna drive the process, but he reports to MedCram that the data is pointing toward the need, more than likely.
Personal Adjustments?
Dr. Topol reminds everyone that we are in the middle of a pandemic, with a highly infectious variant circulating worldwide. He emphasized important personal decisions, from wearing a proper mask when needed—the type that fits snugly—to practicing social distancing. Topol doesn’t think it’s a good idea right now to have indoor gatherings—even if vaccinated. That’s because he doesn’t know if the vaccinated people are infected, and either pre-symptomatic or asymptomatic. In the middle of a severe surge, Topol emphasizes to the viewer that he is waiting to “get to the other end” before assuming any sense of normalcy.
COVID-19 Intranasal Vaccine Pipeline
TrialSite conducted a brief review of the COVID-19 nasal vaccine pipeline, given the importance Dr. Topol awarded this topic. Early on in the process, for whatever reason, they were not considered in the first major vaccine development effort. Only a handful of the total COVID-19 vaccine pipeline includes nasal-centric candidates based on a review of the World Health Organization (WHO) COVID-19 vaccine tracker and landscape.
Out of 112 COVID-19 vaccine candidates worldwide, only eight (8) are nasal-based. While two intranasal investigational products are in Phase 2, one is developed by the University of Hong Kong, Beijing Wantai Biological Pharmacy Enterprise, and Xiamen University in collaboration with the Coalition of Epidemic Preparedness Innovations (CEPI). According to Chinese press Xinhuanet, this candidate is now headed for Phase 3 studies.
A protein subunit vaccine under development in Iran is led by the Razi Vaccine and Serum Research Institute.
The U.S. is home to a couple of intranasal investigational products in Phase 1, including a single dose, nasal vaccine candidate known as AdCOVID. Altimmune, a clinical-stage biotech in the Washington DC-Baltimore biotech corridor, produced positive preclinical research results showing that their intranasal vaccine offered mice 100% protection against a lethal challenge from the SARS-CoV-2 virus.
The company has been collaborating in preclinical with the University of Alabama at Birmingham (UAB) and the laboratory of James Brien, Ph.D., and Amelia Pinto, Ph.D. in the Department of Molecular Microbiology & Immunology at Saint Louis University.
Altimmune’s clinical trial (NCT04679909) evaluates the immune response and safety of AdCOVID administered as an intranasal spray in healthy adults. The study trial is led by trial sites Optimal Research and Clinical Trials of Texas. With 92 targeted participants, the Phase 1 study is scheduled for completion in February 2022.
Trial Site locations include Optimal Research (Melbourne, FL; Peoria, IL; Rockville, MD; Austin, TX) and Clinical Trials of Texas (CTT), which went through a private-equity-led recapitalization.
A live-attenuated candidate developed by Meissa Vaccines demonstrates that the investigational product was effective in preclinical nonhuman primate data. The sponsors reported that in the preclinical research, the candidate “was highly protective” against SARS-CoV-2 in the areas Dr. Topol emphasized in the interview—the upper and lower respiratory tract region. This vaccine candidate was given the greenlight by the FDA for clinical trials in March.
Called MV-014-212, the study (NCT04798001) investigates a live attenuated vaccine against the respiratory syncytial virus (RSV) expressing the spike (S) protein of SARS-CoV-2. The study evaluates the safety of and the immune response to the vaccine when administered to healthy adults between the ages of 18 and 69 years who are seronegative to SARS-CoV-2 and haven’t received a prior vaccine targeting COVID-19.
The study runs through until October 2022 and is led by a Phase 1 trial site called Johnson County Clin-Trials, a research center located in Kenexa, Kansas. The vaccine’s developer, Meissa Vaccines was founded in 2014 and is based in Redwood City, CA, near San Francisco.
India’s Bharat Biotech is developing a non-replicating adenoviral vector candidate. The firm recently completed a Phase 1 study of its candidate known as BBV154, reporting they submitted the data to the India drug regulatory Central Drugs Standard Control Organization (CDSCO). Shortly thereafter, regulators gave the nod for Phase 2/3 trials.
A few months ago, the University of Oxford announced the launching of a clinical trial investigating the delivery of the ChAdOx1 nCoV-19 COVID-19 vaccine using a nasal spray. This is the same vaccine licensed for commercialization by AstraZeneca. The Phase 1 trial focuses on the study of 30 healthy volunteers aged 18 to 40. Investigators, led by Dr. Sandy Douglas, Clinician-Scientist and Chief Investigator, will investigate the level of immune system responses triggered by the investigational vaccine and safety monitoring.
At the start of the year, Serum Institute of India (SII), the biggest vaccine maker by volume worldwide, partnered up with Codagenix to commence a Phase 1 trial of COVI-VAC, a single dose, intranasal live attenuated vaccine for COVID-19.
According to the study disclosure, data should materialize soon. Interestingly, according to the disclosure, human challenge research leader hVIVO serves as the trial site location.
In Cuba, the Center for Genetic Engineering & Biotech has a nasal-focused protein subunit vaccine underway. Thailand will test the Cuban vaccine in a clinical study in addition to a home-grown-based adenovirus vector-based and influenzas virus vector-based COVID-19 vaccines developed by Thailand’s National Center for Genetic Engineering and Biotechnology.
CanSino Biologics, the Chinese venture that failed to deliver Canada’s investigational product for early clinical trials, also recently announced the launching of nasal spray trials. Fortune reported that Chinese regulatory authorities gave the greenlight in March, making CanSino Biologics the only Chinese COVID-19 vaccine maker with approval to conduct nasal spray trials. The vaccine, according to Xinhuanet, was jointly developed by researchers from the Institute of Military Medicine under the Academy of Military Sciences and the company.
