Day: December 3, 2021

Moderna Narrowly Beats Pfizer in Effectiveness

Image of a syringe for vaccination
Photo by Mika Baumeister on Unsplash

In the first head-to-head comparison of the effectiveness of the Pfizer-BioNTech and Moderna COVID vaccines, researchers examined the electronic health records of veterans who had received each vaccine and found Moderna to be slightly more effective.

The Moderna vaccine’s increased level of protection included a 21% lower risk of documented infection and 41% lower risk of hospitalisation, according to the research team, whose findings were published in the New England Journal of Medicine.

“Both vaccines are incredibly effective, with only rare breakthrough cases,” said Dr J.P. Casas, a member of the research team. “But regardless of the predominant strain – Alpha earlier and then Delta later – Moderna was shown to be slightly more effective.”

Researchers designed their comparative effectiveness study to address the previously unanswered question of which of the two mRNA vaccines is more effective. Effectiveness outcomes were: documented COVID, symptomatic disease, hospitalisation, ICU admission, and death. The investigators drew on the database of US veterans who received one of the two COVID vaccines between early January 2021 and mid-May 2021.

As initially designed, the research focused on the Alpha variant that predominated at the time. The study matched 219 842 recipients of the Pfizer vaccine to the same number of recipients of the Moderna vaccine. The two groups were matched based on a variety of clinical and demographic factors that could affect outcomes.

Over the study’s 24-week follow-up period, the estimated risk of documented infection was 4.52 events per 1000 people in the Moderna vaccine group and 5.75 per 1000 in the Pfizer group, an excess of 1.23 cases per 1000. The investigators also observed smaller excesses of symptomatic COVID (0.44 events), hospitalisation (0.55 events), ICU admission (0.10 events), and death (0.02 events) per 1000 people in the Pfizer group relative to the Moderna group.

This pattern of a lower risk for Moderna held up when Delta was the main strain. In this comparison, excess risk of documented infection over 12 weeks was 6.54 events per 1000 people for the Pfizer vaccine, compared to Moderna. Given the shorter time frame available for this supplementary research, infection was the only outcome researchers analyzed. Also, the estimates were considered less precise because a smaller number of individuals were eligible for this analysis.

Randomised trials comparing the mRNA vaccines against placebos had previously shown both vaccines to be very effective against symptomatic COVID infection (95% effectiveness for Pfizer-BioNTech, 94% for Moderna), borne out by real-world vaccine use.

“Given the high effectiveness of both the Moderna and Pfizer vaccines, confirmed by our study, either one is recommended to any individual offered a choice between the two,” said first author Dr Barbra A. Dickerman. “However, while the estimated differences in effectiveness were small on an absolute scale, they may be meaningful when considering the large population scale at which these vaccines are deployed. This information may be helpful for larger decision-making bodies.”

The massive Veteran Association records system supported a very large sample size. This, in turn, allowed the study to identify even small differences in effectiveness between the Pfizer and Moderna vaccines. The researchers used a methodology known as causal inference to mirror a gold standard randomised trial as closely as possible. Causal inference is a type of data analysis that helps researchers draw firm conclusions about cause and effect.

Using the VA database, vaccine recipients were closely matched on age, sex, race, geographic location, and other attributes that could affect COVID-related outcomes.

“After this careful matching, we found that the two vaccine groups were extremely similar in terms of variables with respect to an extensive set of demographic, geographic, and health-related attributes,” Dr Dickerman said. “This allowed our observational analysis to produce exceptionally credible results during a global emergency, when answers are needed fast and randomised trials can be impractical.”

As the global pandemic continues to unfold, the research team is working on answers relating to the comparative safety, versus effectiveness, of the Pfizer and Moderna vaccines. Dr Dickerman characterises comparative safety as an “additional piece of the puzzle to support vaccine decision-making.”

Even beyond this analysis, further evaluation of the vaccines’ comparative effectiveness and safety is needed, the authors concluded. Meanwhile, given the evidence at hand, the authors concluded about the Pfizer and Moderna vaccines considered in their study, “Given the high effectiveness and safety profile of both mRNA vaccines, either one is strongly recommended.”

Source: EurekAlert!

Six Different Booster Vaccines Found to be Safe and Effective

Image by Ivan Diaz on Unsplash

The first randomised trial of COVID boosters, published in The Lancet, has shown that six are safe and provoke strong immune responses. Participants have previously received a two-dose course of ChAdOx1-nCov19 (Oxford–AstraZeneca [ChAd]) or BNT162b2 (Pfizer-BioNTech [BNT]). The announcement comes just as the Omicron variant is beginning to spread around the world.

ChAd has now been deployed in more than 180 countries and BNT in more than 145 countries. Several studies show that two doses of ChAd and BNT confer 79% and 90% protection, respectively, against hospitalisation and death after six months. However, protection against COVID infection wanes in time, which has led to the consideration of boosters. However, there are currently little data on the comparative safety of COVID vaccines, and the immune responses they stimulate, when given as a third dose.

The COV-BOOST study looked at safety, immune response (immunogenicity) and side-effects (reactogenicity) of seven vaccines when used as a third booster jab. The vaccines studied were ChAd, BNT, NVX-CoV2373 (Novavax [NVX]), Ad26.COV2.S (Janssen [Ad26]), Moderna [mRNA1273], VLA2001 (Valneva [VLA]), and CVnCov (Curevac [CVn]).

“The side effect data show all seven vaccines are safe to use as third doses, with acceptable levels of inflammatory side effects like injection site pain, muscle soreness, fatigue. Whilst all boosted spike protein immunogenicity after two doses of AstraZeneca, only AstraZeneca, Pfizer-BioNTech, Moderna, Novavax, Janssen and Curevac did so after two doses of Pfizer-BioNTech”, commented Professor Saul Faust, trial lead.

“It’s really encouraging that a wide range of vaccines, using different technologies, show benefits as a third dose to either AstraZeneca or Pfizer-BioNTech. That gives confidence and flexibility in developing booster programmes here in the UK and globally, with other factors like supply chain and logistics also in play”, added Prof Faust.

“It’s important to note that these results relate only to these vaccines as boosters to the two primary vaccinations, and to the immune response they drive at 28 days. Further work will generate data at three months and one year after people have received their boosters, which will provide insights into their impact on long-term protection and immunological memory. We are also studying two of the vaccines in people who had a later third dose after 7-8 months although results will not be available until the new year.”

A randomised, phase 2 trial of seven booster vaccines was conducted, with the third doses given 10-12 weeks after initial two-dose courses of ChAd or BNT. The trial involved 2878 healthy participants between June 1st and June 30th 2021. Participants had received their first doses of ChAd or BNT in December 2020, January or February 2021, and second doses at least 70 days before enrolment for ChAd and at least 84 days for BNT. About half of participants received two doses of ChAd and half two doses of BNT. The control vaccine used was a meningococcal conjugate vaccine (MenACWY).

Participants were aged 30 or older, roughly half of whom were 70 or older. The average age of participants who received ChAd was 53 years in the younger age group and 76 years in the older age group. Average ages for BNT were 51 and 78 years, respectively.

Thirteen experimental and control arms of the trial (seven vaccines plus three at half dose and three control arms) were split into three participant groups. Group A received NVX, half dose NVX, ChAd, or a control. Group B received BNT, VLA, half dose VLA, Ad26 or a control. Group C received Moderna, CVn (development of which was halted in October 2021), half dose BNT, or a control.

Primary outcomes were adverse effects seven days after receiving a booster, and levels of antibodies targeting the SARS-CoV-2 Spike protein after 28 days, compared to controls. Secondary outcomes included the response of T cells to wild type, Alpha, Beta, and Delta variants. 

Increases in anti-spike protein antibody levels after 28 days varied across the vaccines. After two doses of ChAd these ranged from 1.8 times higher to 32.3 times higher according to the booster vaccine used. Following two doses of BNT, the range was 1.3 times higher to 11.5 times higher. Significant T-cell responses were reported in several combinations.

At 28 days, all booster results were similar for participants aged 30-69 years and those aged 70 years or older. Boost ratios should be interpreted with caution, the authors caution, since they relate to immunogenicity rather than protection against disease, and the relationship between antibody levels at day 28 and long-term protection and immunological memory is unknown.

Reactions to all seven vaccines were similar, with fatigue, headache, and injection site pain most often reported. These were more commonly reported by those aged 30-69. 912 of the 2878 participants experienced a total of 1036 adverse events, 24 of which were severe.

Source: EurekAlert!

Neuromodulation Could Help Heart Muscle Regeneration

Photo by Robina Weermeijer on Unsplash

Human heart muscle cells stop multiplying after birth, making any heart injury later in life a permanent one, reducing function and leading to heart failure. Now, however, researchers have new evidence that manipulating certain nerve cells or their controlling genes might trigger the formation of new heart muscle cells and restore heart function after heart attacks and other cardiac disorders.

The study, published in Science Advances, sheds new light on how some neurons regulate the number of heart muscle cells. While nerve cells have long been known to regulate heart function, their role and impact during heart development and their effect on muscle cell growth has been unclear.

“Our study sought to examine the role of so-called sympathetic neurons on heart development after birth, and what we found is that by manipulating them, there could be tremendous potential for regulating the total number of muscle cells in the heart even after birth,” said lead author Emmanouil Tampakakis, MD, assistant professor of medicine at the Johns Hopkins University School of Medicine.

The nerve cells that make up the sympathetic nervous system (SNS) control automatic processes in the body such as digestion, heart rate and respiration. The SNS is typically associated with ‘fight-or-flight’ responses.

Researchers in this study made a genetically modified mouse model by blocking sympathetic heart neurons in developing mouse embryos, and analysed the drivers of heart muscle cell proliferation through the first two weeks of life after birth.

What they found was a significant decrease in the activity of a pair of genes – the period 1 and period 2 genes – already known to control the circadian cycle. Remarkably, removing those two circadian genes in mouse embryos, the researchers saw increased neonatal heart size and an increase in the number of cardiomyocytes, or heart muscle cells, by up to 10%. Thus, sympathetic nerves on heart muscle cells could likely be mediated through these two circadian genes.

Circadian, or ‘clock’, genes are components of the circadian rhythm pattern that in mammals regulates bodily functions on a roughly 24-hour cycle aligned with hours of daylight and darkness.

“Shortly after birth, mammals, including people and mice, stop producing heart muscle cells. And unlike other organs, like the liver, the heart can’t regenerate after it’s damaged,” said Prof Tampakakis. “We’ve shown that it may be possible to manipulate nerves and/or circadian genes, either through drugs or gene therapies, to increase the number of heart cells after birth.”

Up to a billion heart muscle cells can be lost after a heart attack, and Prof Tampakakis says there is scientific evidence that hearts tend to recover faster after an attack when the total number of cells to begin with is higher. By manipulating sympathetic nerves and clock genes (a technique called neuromodulation) researchers believe the heart could be made to respond to injury much better.

“Neuromodulation is a pretty new concept in cardiology, and we believe these are the first reports that associate clock genes with new growth of heart muscle cells.” saidChulan Kwon, PhD, MS, associate professor of medicine at the Johns Hopkins University School of Medicine. “Our study, maybe for the first time, shows what’s happening if you block the supply of nerves to the heart, and provides new insights for developing neuromodulation strategies for cardiac regeneration.”

Source: Johns Hopkins Medicine