Currently, the development of vaccines for influenza and other viruses typically relies on egg-based manufacturing. This approach, and the newer technique of vaccine production in cell cultures, carry the risk of mutations that may reduce the efficacy and immunogenicity of the vaccines. Additionally, there are ongoing needs for greater production speed and capacity to enable adequate epidemic and pandemic response.
An emerging body of research highlights plant-based vaccine manufacturing as a potential solution to some of these limitations. In a recent issue of the Lancet, investigators from the Research Institute of the McGill University Health Centre in Montreal, Quebec, and Medicago Inc., a Quebec-based biopharmaceutical company, described results of 2 randomized, observer-blinded phase 3 studies evaluating the efficacy of a recombinant quadrivalent virus-like particle (QVLP) influenza vaccine manufactured in Nicotiana benthamiana, a relative of the common tobacco plant.1 These studies represent the first large trials of any plant-derived human vaccine.
One trial tested the vaccine in adults aged 18-64 years (Clinicaltrials.gov Identifier: NCT03301051), while the other trial consisted of adults aged 65 years and older (Clinicaltrials.gov Identifier: NCT03739112) across North America, Asia, and Europe. Participants from both groups were required to be generally healthy at baseline. The studies were conducted during the 2017-2018 and 2018-2019 influenza seasons, respectively.
In the first trial, 5077 individuals were assigned to the QVLP vaccine group and 5083 were assigned to a placebo group. In the final per-protocol analysis, the groups consisted of 4814 and 4812 participants, respectively. The primary outcome was 70% absolute efficacy of the vaccine to prevent “laboratory-confirmed, respiratory illness caused by antigenically matched influenza strains,” which the study did not meet (35.1%; 95% CI, 17.9%-48.7%). Serious adverse events occurred in 1.1% of the QVLP group and 1.0% of the placebo group; 0.1% of each group experienced severe treatment-related or treatment-emergent adverse events.
In the second trial, 6396 participants were assigned to receive the QVLP vaccine and 6398 were assigned to receive a quadrivalent inactivated vaccine (QIV). The final per-protocol analysis included 5996 and 6026 participants, respectively. The primary outcome was the relative efficacy of the QVLP vaccine against laboratory-confirmed influenza-like illness caused by any strain of influenza, which was met with a relative efficacy of 8.8% (95% CI, -16.7% to 28.7%). Serious adverse events occurred in 4.1% of the QVLP group and 4.2% of the QIV group; 0.1% of each group experienced severe treatment-related or treatment-emergent adverse events.
These results indicate that while the “QVLP vaccine did not meet the success criterion for its primary endpoint in the 18-64 study, [the] vaccine can provide substantial protection against respiratory illness and influenza-like illness,” the authors concluded. Vaccine efficacy estimates are similar to other licensed vaccines on the market. The findings also indicate that the vaccine was well-tolerated, with a favorable safety profile in both studies.
In addition to the influenza vaccine evaluated in these trials, Medicago Inc. recently reported promising phase 1 results of a similar produced vaccine candidate for severe acute respiratory virus coronavirus 2 (SARS-CoV-2). To combat the coronavirus disease 2019 (COVID-19) pandemic, Medicago Inc. stated that their vaccine “induced robust neutralizing antibody and cellular immune responses” after 2 doses, as stated in a press release.2 “The Coronavirus-Like Particle COVID-19 vaccine candidate (CoVLP) is composed of recombinant spike (S) glycoprotein expressed as virus-like particles (VLPs).” The company is now conducting phase 2/3 trials of CoVLP using GlaxoSmithKline’s proprietary pandemic adjuvant and plans to submit results for regulatory review in 2021.3,4
To learn more about plant-derived vaccine manufacturing, we interviewed Ed Rybicki, PhD, professor and director of the Biopharming Research Unit in the Department of Molecular and Cell Biology at the University of Cape Town in South Africa. His team has been investigating these technologies for nearly 2 decades.
What does plant-based manufacturing of vaccines involve, and what are some of the benefits of this method?
Dr Rybicki: This is a big subject, but basically it involves using plants (usually N benthamiana) to produce the essential proteins needed in a subunit vaccine. This is done either by making the plants transgenic with a foreign gene inserted into the genome or – much more often lately – by using a bacterium called Agrobacterium tumefaciens to transfer recombinant DNA encoding gene(s) of interest into normal plants for transient expression.
The advantage of this technique is that one can go from having a gene sequence – for example, SARS-CoV-2 S protein – to having lots of protein in the time it takes to synthesize a gene, clone it into Agro, grow up a small volume of Agro, and use it to put the gene into a large number of plants (which could be kept as standby biomass, as they’re cheap to grow) to give you protein a week or so later. Medicago Inc. did this for SARS-2 S in 20 days or so.
Benefits include the most rapid scale-up time for any production method, very rapid preparation of cloned DNA to do it with, and far cheaper upstream costs compared to any of the stainless steel fermentation methods. So, this is a good pandemic response technology!
What is the significance of the current findings by Ward, et al?
Dr Rybicki: The findings suggest that a plant-made candidate 4-valent seasonal influenza vaccine is at least equivalent to conventional egg-made vaccine, and quite possibly better in terms of eliciting cellular responses because of its nature as virus-like particles instead of subunit proteins. There are no viable VLP-based flu vaccines available that are made in any other way. The clinical trial results established the Medicago flu vaccine candidate as a viable alternative to conventional offerings, and moreover, one that can be very quickly tailored to account for changes in circulating influenza virus strains, unlike egg production which involves a 6-month turnaround.
What are the potential implications of this technology for future vaccine manufacturing?
Dr Rybicki: The potential implications are that subunit vaccines, including for hepatitis B as well as papillomaviruses, which we have worked on here (HPV), may be more cheaply and conveniently produced in plants because proofs of concept already done. In addition, the flexible scaling of production volume may be a significant benefit in pandemic and epidemic response compared to conventional manufacturing methods. Plant-based vaccine manufacturing could possibly expand the range of candidate human and animal vaccines available and to enhance the rapid response capability.
Disclosure: Ed Rybicki, PhD declared affiliations with Medicago Inc.
References
1. Ward BJ, Makarkov A, Séguin A, et al. Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18-64 years) and older adults (≥65 years): two multicentre, randomised phase 3 trials. Lancet. 2020;396(10261):1491-1503. doi:10.1016/S0140-6736(20)32014-6
2. Medicago. Press release: Medicago announces positive phase 1 results for its COVID-19 vaccine candidate. Published online November 10, 2020. Accessed online January 4, 2021.
3. Medicago. Press release: Medicago and GSK announce start of phase 2/3 clinical trials of adjuvanted COVID-19 vaccine candidate. Published online November 12, 2020. Accessed online January 4, 2021.
4. Medicago. Medicago’s development programs: COVID-19. Accessed online January 4, 2021.
Additional Suggested Reading
1. Rybicki EP. Plant molecular farming of virus-like nanoparticles as vaccines and reagents. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2020;12(2):e1587. doi:10.1002/wnan.1587
2. Rybicki E. Plant-made vaccines and reagents for SARS-CoV-2 in South Africa. ViroBlogy. Accessed online January 4, 2021.
3. Rosales-Mendoza S, Márquez-Escobar VA, González-Ortega O, Nieto-Gómez R, Arévalo-Villalobos JI. What does plant-based vaccine technology offer to the fight against COVID-19? Vaccines (Basel). 2020;8(2):183. doi:10.3390/vaccines8020183
4. Rockman S, Laurie KL, Parkes S, Wheatley A, Barr IG. New technologies for influenza vaccines. Microorganisms. 2020;8(11):1745. doi:10.3390/microorganisms8111745
5. Dhama K, Natesan S, Iqbal Yatoo M, et al. Plant-based vaccines and antibodies to combat COVID-19: current status and prospects. Hum Vaccin Immunother. 2020;16(12):2913-2920. doi:10.1080/21645515.2020.1842034
This article originally appeared on Infectious Disease Advisor
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Tri-sets are similar to supersets except with three workouts back
to back to again. And Mega-sets are 4+ exercises one after another,
after another. One things they all had in widespread although was that they
trained with intensity.
Sticking with a program for 12 weeks will permit you to maximize your power and muscle building potential.
However you’re going to notice that your reps are going to increase during this
phase. You see, the old school guys didn’t have the state-of-the-gym gym tools we’ve at present.
When you are young, and completely naive to resistance coaching and also
you first begin, there is an argument for having a large surplus.
A newbie who’s relatively high in physique fats will in all probability be capable of maximize hypertrophy at maintenance or even potentially in a small deficit,
although there are some limits to that. If you’re somebody
who’s starting comparatively high in body fat, you’re
probably not going to wish to be in a calorie surplus.
When it comes to how to build muscle, you definitely do not
have to be in a calorie surplus. However I
assume after a couple of weeks of them figuring out how to do a full range movement, that they’re primarily good
to go as far as just like the partials go. And actually, as much as scientists don’t like to say it, most of
these research are done in relatively untrained populations.
The ethical of this story is that the toughest coaching will yield the most
metabolic stress. So you’ll do one set of 1A, rest,
then one set of 1B, relaxation again, and repeat till all units are complete.
Carry Out the remaining workouts as regular straight units.
Not even pro bodybuilders with skilled coaches and enough medicine in their our
bodies to produce a pharmacy peak completely on a daily basis.
It requires exhausting work and dedication, but nearly anyone can enter a bodybuilding competition and be pleased with their
results on stage. In bodybuilding competitions, athletes are judged on their muscularity, definition, symmetry, and
overall physique.
When correctly applied, this program will work for any age group.
These with pre-existing well being situations or accidents may have to select and choose workouts primarily based on bodily limitations.
We pride ourselves on using our years of expertise and research in the area of well being and health to help others attain their health goals.
For example, let’s say that you’re doing barbell curls –
your common weight with which you are capable of
doing 8 repetitions is 45lbs. So, am going to use their exercise program, then I will turn into muscular”.
Key measures embrace weight, look, skinfolds, energy, mood, and health. Your ultimate four weeks are going to shift slightly into gaining more muscle definition whereas maintaining the mass you’ve gained and maybe gaining even more dimension. This is essential as a result of, without proper restoration, you won’t make features. You’ll focus solely on your quads for most of your exercise. This will allow you to put your whole vitality into constructing huge quads.
The number of reps you carry out is only as effective as the trouble you set into each set. You want to ensure you take every rep via a whole range of movement and that you’re lifting simply wanting technical failure (when you can’t full one other rep with textbook form). If you’ve ever seemed for a solution to this query, you’ve probably been instructed to raise between one and 5 reps for strength, eight to 12 for muscle, and 15-plus for endurance. The ‘push-pull-legs’ exercise idea has been round endlessly.
Whereas individual protein wants will differ from individual to individual, there’s a common guideline for the quantity of protein you should be consuming day-to-day. It is really helpful, if your objective is development, to consume a minimal of one gram of protein per pound of bodyweight every day. For the “hardgainer” and extra superior bodybuilder, it may be necessary to ingest as much as 2 grams per pound. Myofibrillar hypertrophy, on the other hand, is an actual improve in the dimension of the muscle contractile fibers. This is extra everlasting and can point out actual muscle dimension features. It’s slower to return about, but when it does, it’s more likely to stand the test of time. This type of development is noted extra after heavy weight units of between 4-10 reps.
The program requires a considerable time dedication, as it involves six days of training each week. You Will want to gauge if your schedule can deal with this degree of dedication without affecting other areas of your life. Physically, the workout demands lots from your physique, so it’s important to ensure you’re capable of dealing with intense workouts and haven’t any current situations that might worsen. Quick restoration can additionally be essential, as every muscle group has a comparatively short relaxation interval before being labored once more. Arnold Schwarzenegger’s coaching philosophy is centred across the elementary aim of building important muscle mass.
This will maintain the stress on the pecs throughout the entire motion. That will present your body with 48 hours to relaxation, get well and grow between each training session. So, in Week One, you’ll train on Monday, Thursday and Sunday. Even though this does not provide you with a set day to train every week, it does give you the best coaching frequency. Weight loss relies upon burning extra calories than the quantity consumed over time. Any exercise program can help with burning energy, however the other important part of this equation is food regimen. If you eat sufficient, you presumably can acquire weight while running a lifting program.
You don’t should weigh every thing you eat and calculate grams and energy precisely. When you’re trying to construct muscle, somewhat too much meals won’t hurt, but not getting sufficient can stop you from seeing the results you need. Lifting weights inform your muscles to develop bigger and stronger. Nonetheless, they can’t achieve this without proper quantities of energy and nutrients. You build muscle each within the fitness center and within the kitchen, and you can’t ignore both if you would like good results.
Some individuals have naturally massive calves without training them, while others discover it extremely exhausting and a waste of time to train calves because they simply don’t respond. You see this phenomenon even amongst skilled bodybuilders. You’ll be doing three sets of 12 reps of leg extensions. Maintain the muscle pressure throughout the whole movement by reducing the burden beneath management and contracting your quads on the high. Squat-type workout routines are the mass- and power builders of your leg training, and by including leg extensions, you lay the inspiration for optimal quad growth. After two or three warm-up units, perform 5 working sets with a rep range of 6 to 12, growing the burden you use set by set. You can see the precise set configuration within the StrengthLog app.
Choose a weight that allows you to squat closer to 8 instances before utterly fatiguing, but do not truly squat eight occasions. I used major compound lifts which would possibly be finest for enhancing strength and constructing muscle. In addition, I’ve integrated no much less than one exercise from each main movement sample. One major distinction you’ll notice is you’re typically going backwards and forwards between totally different muscular tissues. For instance, in the first workout, you’ll do your 5 sets of squats then go to your primary shoulder train. As it’s a high-intensity routine, the duo advises choosing a medium weight for this session. You wish to select a load that’ll challenge your muscles to get by way of a set, however won’t have an result on your kind.
You can use our calorie calculator under to estimate how many energy you need. It relies on the Mifflin-St Jeor equation, some of the accurate formulation. Enter your intercourse, weight, peak, age, and estimated exercise degree. It will calculate your maintenance energy (the complete caloric intake you want in your body weight to be stable). Additionally, because you do many units for every muscle, your set quality would possibly undergo towards the end of your training sessions.
Supersets hold your coronary heart fee up and enhance conditioning. You additionally sweat and breath heavy when training supersets. You burn more calories and work more muscle in much less time.
In that case, I suggest at least 1.8 grams per kg (0.8 grams per pound) to take care of or even gain lean physique mass whereas shedding fat. Advanced energy athletes will wrestle to add muscle while cutting, however you might have the advantage here as a result of you’re new to bodybuilding. You are much more likely to gain lean muscle whereas losing physique fat, giving you the most effective of both worlds. The leg curl isolates your hamstrings and completely complements the Romanian deadlifts in exercise A of Bodybuilding for Novices. It’s necessary you prepare the back of your legs with the same effort you prepare your quads, as even aggressive bodybuilders typically lack hamstring growth. Primarily a shoulder train, the overhead press additionally works your chest, triceps, and core muscle tissue, making it an excellent general compound motion for dimension, energy, and stability.
For the other workouts do not work until complete failure, cease at least 1-2 reps short. Work on progressively increasing repetitions each session and eventually load, once you have reached the top of the allotted range. Include workout routines, units, reps, size of exercise, resting intervals, etc. Leg day is heavy within the squat category to hit the entire leg musculature sufficiently (quads, hamstrings, glutes). You’ll start off with entrance squats and leg extensions, blasting the entrance quads.
The precise variety of exercises it takes to achieve this point will differ from individual to individual, and from train to train. You need to give your muscles a reason to get bigger, or you’ll stay stuck on the identical size you’re proper now. The variety of units listed are the actual work sets solely, and don’t embody warm-up sets. Not Like the incline curl, which emphasises the lengthy head of the biceps, the preacher curl works higher for recruiting the short head of the muscle. If you don’t have a preacher curl bench, concentration curls do an analogous job. One of the features of the pecs is to draw the arms across the body in a hugging-type motion, which is exactly what you get with the cable crossover.
They fed off each others power and each needed to hold the Sandow trophy on high of the rostrum. The heavy weight wakes up the nervous system and get you firing on all cylinders. A good instance is the conventional squat, held in reverence as a quad train. The drawback is that the quads are the primary mover for under a portion of the squat, with the glutes and lower again liable for transferring an excellent percentage of the load. There are dozens of workouts you are able to do for a body half; we had to attract the line somewhere. Do the subsequent set when you are able to do it with equal or higher intensity [as the one you just did].
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Introduction
Understanding the basics of performance-enhancing steroids can be overwhelming, but let’s break it down step by step. In this guide, we’ll focus on three popular steroids: Testosterone, Anavar, and Dianabol. We’ll cover their uses, effects, and considerations for users.
Understanding Testosterone
What is Testosterone?
Testosterone is a naturally occurring hormone in the body, primarily responsible for building muscle, maintaining libido, and promoting overall health.
Role of Testosterone
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