RNA vaccines are efficient preventive measures to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the IgG response mainly consists of the pro-inflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of non-inflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose on average from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B-cell population (median 14.4%; interquartile range (IQR) 6.7–18.1%) compared to the overall memory B-cell repertoire (median 1.3%; IQR 0.9–2.2%) after three immunizations. Importantly, this class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Since Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2.
Speaking this week on The Mail on Sunday’s Medical Minefield podcast, Prof Woolhouse said: ‘I think that lockdown will be viewed by history as a monumental mistake on a global scale, for a number of reasons.
‘The obvious one is the immense harm the lockdown, more than any other measure, did in terms of the economy, mental health and on the wellbeing of society.
…[A study published in Science in February 2021] also found something intriguing: lockdowns could, in a worst-case scenario, actually increase transmission of the virus by up to five per cent.
…As Dr Ali puts it: ‘Some people say lockdowns were beneficial, others that they were really terrible.
‘The reality actually is much closer to the idea that it didn’t make much difference either way.’
For those who made painful sacrifices, that won’t be an easy truth to swallow.
Science journals have encouraged and enforced a false Covid narrative
Bear in mind that in the heat of this pandemic, papers printed in important journals were peer-reviewed within 10 weeks; one rattled through the process in just nine days for Nature. But, like Petrovsky, I have heard similar stories from many other frustrated experts who confronted the conventional wisdom that this lethal virus was a natural spillover event. Some could not even get letters published, let alone challenge those key papers promoting the Chinese perspective which have since turned out to be flawed or wrong.
Only now is acceptance emerging that the science establishment colluded to dismiss the lab leak hypothesis as a conspiracy theory, assisted by prominent experts with clear conflicts of interest, patsy politicians and a pathetic media that mostly failed to do its job. And yet, at the heart of this scandal lie some of the world’s most influential science journals. These should provide a forum for pulsating debate as experts explore and test theories, especially on something as contentious and fascinating as the possible origins of a global pandemic. Instead, some have played a central role in shutting down discussion and discrediting alternative views on the origins, with disastrous consequences for our understanding of events.
For a virus that spreads via airborne transmission of aerosols—something scientists have known for many months, though it took the World Health Organization until the end of April to update its guidance—these plastic barriers between diners were always a confusing addition. Think of the particles that disperse through the air when someone smokes a cigarette. A plastic barrier wouldn’t prevent you from smelling that cigarette and breathing some of that same air.
Most people will escape “severe” side effects, defined as those that prevent daily activity. Fewer than 2% of recipients of the Pfizer and Moderna vaccines developed severe fevers of 39°C to 40°C. But if the companies win regulatory approvals, they’re aiming to supply vaccine to 35 million people worldwide by the end of December. If 2% experienced severe fever, that would be 700,000 people.
Other transient side effects would likely affect even more people. The independent board that conducted the interim analysis of Moderna’s huge trial found that severe side effects included fatigue in 9.7% of participants, muscle pain in 8.9%, joint pain in 5.2%, and headache in 4.5%. In the Pfizer/BioNTech vaccine trial, the numbers were lower: Severe side effects included fatigue (3.8%) and headache (2%).
But that’s a higher rate of severe reactions than people may be accustomed to. “This is higher reactogenicity than is ordinarily seen with most flu vaccines, even the high-dose ones,” says Arnold Monto, an epidemiologist at the University of Michigan School of Public Health.
The engines of the SARS-CoV-2 pandemic—household and residential settings, community, and long-distance transmission—have important implications for control. Moving from international to household scales, the burdens of interventions are shared by more people; there are few international travelers, but nearly everyone lives in households and communities. Measures to reduce household spread may appear particularly challenging, but because they directly affect so many, they need not be perfect. Household mask use and partitioning of home spaces, isolation or quarantine outside the home, and, in the future, household provision of preventive drugs could have large effects even if they offer only modest protection. Conversely, control measures at larger spatial scales (for example, interregional) must be widely implemented and highly effective to contain the virus. Indeed, few nations have managed to curb infection without stay-at-home orders and business closures, particularly after community transmission is prevalent.
Certain COVID-19 vaccine candidates could increase susceptibility to HIV, warns a group of researchers who in 2007 learned that an experimental HIV vaccine had raised in some people the risk for infection with the AIDS virus. These concerns have percolated in the background of the race for a vaccine to stem the coronavirus pandemic, but now the researchers have gone public with a “cautionary tale,” in part because trials of those candidates may soon begin in locales that have pronounced HIV epidemics, such as South Africa.
Some approved and experimental vaccines have as a backbone a variety of adenoviruses, which can cause the common cold but are often harmless. The ill-fated HIV vaccine trial used an engineered strain known as adenovirus 5 (Ad5) to shuttle into the body the gene for the surface protein of the AIDS virus. In four candidate COVID-19 vaccines now in clinical trials in several countries, including the United States, Ad5 similarly serves as the “vector” to carry in the surface protein gene of SARS-CoV-2, the viral cause of the pandemic; two of these have advanced to large-scale, phase III efficacy studies in Russia and Pakistan.
In today’s issue of The Lancet, four veteran researchers raise a warning flag about those COVID-19 vaccine candidates by recounting their experience running a placebo-controlled AIDS vaccine trial dubbed STEP. An interim analysis of STEP found that uncircumcised men who had been naturally infected with Ad5 before receiving the vaccine became especially vulnerable to the AIDS virus. The vaccine, made by Merck, had been the leading hope for what was then a 20-year search for a shot that could thwart HIV. But after the STEP results appeared, the field went into a tailspin. “It took a decade to recover,” says one of the co-authors of the Lancet correspondence, Lawrence Corey of the Fred Hutchinson Cancer Research Center.
Over long periods of time, social isolation can increase the risk of a variety of health problems, including heart disease, depression, dementia, and even death. A 2015 meta-analysis of the scientific literature by Julianne Holt-Lunstad, a research psychologist at Brigham Young University, and colleagues determined that chronic social isolation increases the risk of mortality by 29%.
A prominent pediatrician and medical researcher in the Philippines has been indicted over the failed—and many say premature—introduction of Dengvaxia, a vaccine against dengue that was yanked from the Philippine market in 2017 because of safety issues. If convicted of accusations leveled at her by the national Department of Justice (DOJ), Rose Capeding, 63, former head of the dengue department of the Research Institute for Tropical Medicine (RITM) here, could face up to 48 years in prison.
…Halstead’s concerns proved valid. In November 2017, Sanofi Pasteur announced that the vaccine could indeed exacerbate cases of dengue in children never previously infected, and the Philippines halted the campaign immediately. (WHO now recommends the vaccine be used only after a test to be sure children have had at least one brush with dengue.)
Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal—but not adult—GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.