Arc cov

Yesterday, Bungie listened to fans and went back to talking about its big Destiny 2 subclass changes early, rather than just dropping them in the live game like they did with Solar 3.0. With Arc 3.0’s reveal , while we didn’t get every single damage value, cooldown and fragment, we got a ton of information, and I figured it was probably wise to make an “Arc 3.0 for dummies” post here to sum up some of the most important things that were revealed.

KEYWORDS – All the new subclasses have buff and debuff keywords that are key to how the aspects and fragments function. Arc is unique in that it has one separate from all of those.

Amplified – All Guardians can get this buff when defeating multiple enemies with arc damage. This boosts your speed (twice, if you keep sprinting) and weapon handling, and will feed into other triggers through aspects and fragments. You also gain damage resistance while sprinting in PvE and it enables a super-slide.

Blind – A debuff to enemies that makes them unable to see or fire their weapon in PvE, in PvP players will get whited out and have a washed-out audio effect.

Jolt – Jolted enemies that get damaged will send out slivers of chain lightning to nearby enemies.

Ionic Traces – All classes have potential access to these, which add energy to your abilities.

Hunter Arc 3.0

Hunters are getting a brand new Arc super, The Gathering Storm, which has them throw their staff down which does initial damage, but creates a damaging AOE field, sending out arcs of lightning to any enemies moving near it.

Aspects:

• Flow State – Defeating a jolted opponent will make you amplified. When you’re amplified, your dodge recharges faster, you’re resistant to damage and you reload faster.
• Tempest Strike – The sliding melee from the current kit, only it jolts enemies now.
• Lethal Current – After dodging, Hunter melee range is increase and it jolts the target, creating a lightning aftershock. During super, after dodging, your next light attack hits twice. Hitting a jolted enemy blinds them.

Finally, Hunters are getting blink back as a jump option, and blink has gotten some generalized buffs to scale back previous nerfs (this also applies to void Warlock).

Warlock Arc 3.0

Being amplified modifies Warlock abilities like its melees. When amplified, its ball lightning attack pulses three times instead of just once. Its Chain Lightning jumps to twice as many enemies. Warlock supers are staying the same, except Stormtrance combines past abilities to be able to both teleport and use Landfall.

Aspects:

• Arc Soul – A cast rift generates an arc soul. When amplified, that arc soul is supercharged, increasing its rate of fire.
• Lightning Surge – Creates a sliding melee where the Warlock transforms into a ball of lightning, teleporting forward and calling down a field of lightning bolds at the exit point that jolts targets.
• Electrostatic Mind – Arc ability kills and kills on blinded or jolted enemies create Ionic Traces. Ionic Traces make you amplified.

Titan Arc 3.0

They are getting a new Thrust class ability. On the ground, double tapping a button bursts in their throttle direction, performing a quick first person evade.

Titans are getting a new melee ability, Thunderclap, where when stationary, you can charge up a punch that can either be a quick strike, you can charge it up further for huge damage.

Aspects

• Touch of Thunder – Boosts to different arc grenades. Flashbang has a second blind pulse, Pulse creates an ionic trace and gets more damage over time. Lightning gets two charges and jolts targets. Storm creates a roaming thundercloud that tracks enemies like Silence and Squall, and zaps them with lightning.
• Juggernaut – When sprinting and with full class ability energy, Titans get a shield that blocks damage, and it’s stronger when amplified. If the shield is broken your class ability is spent.
• Knockout – Melee kills trigger health regen and make the Titan amplified. Critically wounding an enemy or breaking their shield increases melee range and damage. Titan’s base melee is arc-powered when Knockout is active.

Fragments – These are the only one that we know right now, but they are pretty significant, especially this first one:

• Spark of Beacons : When the player is amplified, Arc special weapon kills create a blinding explosion.
• Spark of Resistance: When surrounded by enemies, the player has increased damage resistance.
• Spark of Momentum: Sliding over ammo will reload your weapon and grant a small amount of melee energy. Sliding over Heavy ammo increases the amount of energy granted.
• Spark of Shock: The player’s Arc grenades jolt enemies.

So, those are the highlights, start planning your builds accordingly.

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Vaccines are integral to our control of Covid-19—if not for preventing infection, at least for preventing severe illness and death. But what if vaccine-induced immunity lost its efficacy against new variants on all accounts? Along with earlier work published by MIT, a recent study from Cardiff University places this thought into the realm of possibility. In their paper, Dolton et al. investigate the origins of a SARS-CoV-2 spike protein mutation and its impacts on T cell immune responses in recovering Covid-19 patients and vaccine es. Their analysis revealed that the SARS-CoV-2 spike protein mutation appears invisible to CD8+ T cells, thus dodging immune responses from previous infection and vaccines.

About the Study

Immune mechanism: CD8 T cells

The efficacy of vaccines depends on adaptive immunity, the ability of the body to recognize organisms and structures not previously encountered. Adaptive immunity can be split into two classes: humoral immunity driven by antibodies, and cell-mediated immunity driven by “helper” CD4 T cells and “killer” CD8 T cells. While both contribute to the body’s adaptive immune mechanisms to counter foreign invaders, in the context of the Covid-19, cell-mediated immunity seems the more necessary component to SARS-CoV-2 recovery.

Current understanding dictates that much of the body’s ability to prevent infection comes from the humoral response; it’s now been very well documented that successive variants of SARS-CoV-2 evade by mutations primarily in the Spike protein. Each one of these successive waves of new infections allow the virus to infect people who were previously infected as well as evade the waning immunity such as provided by vaccines. However, these vaccines have proven effective in dramatically reducing, but not entirely eliminating, serious illness requiring hospitalization and death. The ability of vaccines to do so is thought by most researchers to be the result of recognition and clearance of the virus through cell-mediated immunity, primarily through CD8+ killer T cells.

For this study, Dolton et al. focused solely on CD8+ T cell responses. Cell-mediated mechanisms differ from that of humoral immunity. Unlike antibodies, cytotoxic T cells cannot bind and recognize antigens directly. They require antigen presenting cells (APC) to break down foreign proteins into smaller protein fragments and to present the resultant peptides on its cell surface for T cells. Major histocompatibility complexes (MHC) present the resulting peptides to the cytotoxic CD8+ T cells. MHC class I molecules present to cytotoxic CD8+ T cells in particular. Here, the investigators examined killer T cell responses through the most prevalent MHC class I allele in humans—HLA A*02—which occurs in 40% of individuals.

Spike Epitope Mutation P272L

After selecting their scope—CD8+ T cell responses observed through the HLA A*02 allele—the researchers identified which SARS-CoV-2 protein mutation to investigate. Considerations began in people recovering from Covid-19. One study revealed that the most frequent CD8 T cell responses in HLA A*02+ convalescent patients recognized regions of the virus within Spike residues 261-280, as well as ORF1ab residues 3,881-3,900. From this pool, Dolton et al. selected Spike residues 269-277 (YLQPRTFLL) for analysis. The most prevalent mutation in this T cell epitope is an amino acid substitution of proline for leucine, denoted as YLQ L RTFLL or P272L mutation.

Study Results

Tracking the P272L Spike protein mutation

The next step entailed contextualizing mutation P272L by noting its first appearance and frequency in several SARS-CoV-2 variants. The team compared global genome sequencing datasets of Spike residues 269-277 starting from January 1st, 2022 through the course of the pandemic.

They found that the two most frequently occurring mutations in this region occurred at position 272, with P272L widely distributed internationally. The mutation was first detected in lineages B1 and B.1.1.263 of March 2020; by June 2020, it appeared in B.1.177 and spread extensively throughout Europe (as shown in Figure 3).

Additional analysis revealed the P272L mutation recurred frequently and independently in other variants. Dolton et al. report that P272L ranked in the top 15 Spike mutations observed globally. In 2022, P272L spontaneously arose in variants of concern including B.1.1.7/Alpha, B.1.351/Beta, B.1.617.2/Delta, P.1/Gamma, and BA.1/Omicron. The mutation also transmitted locally. Examples include Campania, Italy and Nebraska, USA. Variants carrying the mutation comprised 32% and 29% (respectively) of reported sequences between February 2021 to June 2021.

T cell immune response in convalescent patients and vaccinees

With the epidemiological context established, the question remained: how important is Spike epitope YLQPRTFLL? The investigators sought the answer in two ways: by comparing T cell responses to the founder and variant epitopes in convalescent patients; and by comparing T cell responses to the founder and variant epitopes in vaccinees with no prior history of Covid-19.

To accomplish the first objective, the researchers recruited healthcare workers who had Covid-19 more than 28 days before sample collection in 2020. A polymerase chain reaction (PCR) test confirmed the status. The donors were screened for HLA A*02+ through antibody staining.

The team confirmed the wide response to the epitope, as twelve out of the thirteen patients who tested positive for HLA A*02+ also had CD8 T cells stained with HLA A∗02:01-YLQPRTFLL tetramer. In contrast, the P272L mutant failed to elicit a response. The YLQ L RTFL tetramer did not stain T cells in four convalescent patients. Moreover, a T cell line created from tetramer+ patients did not respond to the mutant despite more than 128 different T cell receptors. Surrogate infected cells with full-length spike and the P272L substitution also failed to recognize T cell clones, supporting the hypothesis that mutant P272L escapes all T cell receptors raised against the Wuhan sequence—a troubling find, as the Wuhan spike is the antigen in all current vaccines.

Dolton et al. also tested T cell responses in vaccinated individuals with no history of Covid-19 and screened positive for HLA A*02+. All seven vaccinees received either the AstraZeneca (ChAdOx1 nCoV-19) vaccine or the Pfizer (BNT162b2 2) vaccine. All participants had T cells which recognize the founder epitope—but do not recognize the P272L mutation.

While it is possible that previously infected or vaccinated individuals could raise an entirely new response to the P272L Spike mutant, and that the YLQLRTFLL sequence could fall into a naïve TCR repertoire “blind spot” that most individuals cannot recognize, Dolton et al. ultimately conclude that T cells specific to spike epitope 269–277 cannot recognize the P272L spike. This, in turn, suggests that such a mutant could escape immunity induced from current interactions of AstraZeneca and Pfizer vaccines.

Possible Implications

The emergence of a T cell escape variant of concern may be impending. The studies of Naranghai et al. and Dolton et al. reaffirm this possible peril. Mutation P272L increased in frequency in B.1.177, and emerged independently in other SARS-CoV-2 lineages. Eventually, a T cell escaping mutation could confer a strong selective advantage. As Dolton et al. mention in their work, “As the pandemic progresses, and SARS-CoV-2 reaches an optimal position with regards to ACE2 binding and cell entry, it is likely that other selective advantages (such as T cell escape) will become more important in the mix of potential advantages that the virus could develop to enable it to persist as a human pathogen.”

What of our best protections against Covid-19, vaccines and immunity from prior infection? These defensive measures may already be weakening. Evidence from Naranbhai et al. suggests that spike mutations in Omicron variant B.1.1.529 can reduce protection in about 21% of people previously infected and/or vaccinated. And should P272L or a similar variant emerge, we can expect even more T cell evasion than already exists.

Given this data, it would be advisable to monitor Spike epitope 269–277 and other viral proteins (ex: ORF1ab residues 3,881-3,900) for possible T cell escape. And Covid-19 vaccines, despite their ability to drastically reduce hospitalization and death, are not impervious to the threat of antigenic variation of SARS-CoV-2 spike. In the future, boosters may need to be altered to anticipate variants primed for T cell escape.

Full coverage and live updates on the Coronavirus

After promising results from a Phase 2 clinical trial , Moderna is now planning to recruit 30,000 people for the next stage of testing of its COVID-19 vaccine.

In a study published in the NEJM , researchers announced the candidate vaccine mRNA-1273 appeared to prompt an antibody response that neutralized the SARS-CoV-2 virus, which causes COVID-19. The trial included 45 healthy adults aged between 18 and 55 years old.

They received two vaccines, 28 days apart, with participants given different doses. The antibody response was found to be higher among those who received a higher dose after the first injection. However, after the second dose, serum-neutralizing activity was reported in all participants.

The vaccine development is being supported by the National Institute of Allergy and Infectious Diseases (NIAID). It aims to create antibodies that can neutralize the virus at its “spike protein.” This is the spiky outer layer seen in images of the virus that help it enter a host cell.

A recently published analysis showed the spike protein of SARS-CoV-2 is far more stable than its closest known relative, and is able to bind to human cells around 1,000 tighter.

In a statement, the NIAID said the vaccine will now move to Phase 3 clinical trials. This is the stage of drug development where a product has been deemed safe and efficient in smaller human trials, so now moves to larger groups of people for testing. In the Phase 2 trial, no serious side effects were found.

Over half of participants reported headaches, fatigue, chills and pain at the injection site. These symptoms were more common after the second injection and among those who received the higher dose.

The NAIAD says plans are now “underway” to start the trial this month. A trial has now been posted to the National Institutes of Health’s clinical trials website on July 14. It says it will enroll an estimated 30,000 participants for a randomized trial, with participants either given the vaccine or a placebo. The trial is expected to begin on July 27 and end on October 27.

To be eligible to enroll, people must be over the age of 18 and healthy. They must be at risk of SARS-CoV-2 infection. Women must not be pregnant and must agree to use contraception throughout the study period. They must also not be breastfeeding. Men must refrain from sperm donation from the point of the first dose and for three months before enrollment.

People not eligible to join include those who have already been infected with SARS-CoV-2, people who are acutely ill, have previously been infected with the coronaviruses MERS-CoV and SARS.

Trials will be taking place at 87 locations across the U.S.. A full list can be found at the end of the NIH’s clinical trial page , along with contact details for Moderna’s clinical trials. Researchers are not yet recruiting for the trial. More details will become available on how to enrol once recruitment opens. Further information on the trial will also be available via Moderna’s COVID-19 vaccine page .

You can also register interest in volunteering for clinical trials of COVID-19 vaccines under development via the NIAID here . The COVID-19 Prevention Network has been set up to combine four clinical trial networks dedicated to the new coronavirus, including the Moderna trial.

THE FIRST Covid vaccine that targets the Omicron variant has been approved by UK drug regulators.

Millions of Brits will receive it next month after the Medicines and Healthcare products Regulatory Agency gave the green light to use Moderna’s updated jab as a booster shot.

Scientists say it will improve immunity because half the vaccine targets the original coronavirus strain and the other half targets Omicron.

Omicron has been dominant in the UK since December 2021.

There have been various strains of the super-infectious bug, including BA.1 (December/January) and BA.2 (spring).

Currently BA.4 and BA.5 are dominant, causing some 4,000 cases per day.

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Although not an exact match to the current variants, the new vaccine is close enough to give a “significantly higher” immune response, Moderna said.

The MHRA said that a clinical trial showed boosting with the bivalent Moderna vaccine triggered a strong immune response against BA.4 and BA.5 as well as against BA.1 and the original strain.

The NHS will now use it for the autumn booster rollout, which will begin in just two weeks’ time.

All over-50s and high-risk groups – a total of 26million people – will be offered a top-up ahead of winter.

Omicron-specific jabs will be given out as standard, with regulators also reviewing a new version of the Pfizer vaccine, while the originals are available as a back-up.

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Health Secretary Steve Barclay said: “Vaccines remain our best defence against Covid and this safe and effective vaccine will broaden immunity and potentially improve protection against variants as we learn to live with this virus.”

Dr Mary Ramsay, of the UK Health Security Agency, added: “Although cases of Covid-19 are relatively low now, we are expecting to see it circulating more widely during the winter months.

“By taking up the booster vaccine this autumn you will increase your protection.”

The antibody boost is expected to further reduce the risk of hospitalisation and death – plus offer better protection against transmission.

It may also build defences ahead of future variants if they have similar mutations to Omicron.

Dr June Raine, CEO of the MHRA, said: “This bivalent vaccine gives us a sharpened tool in our armoury to help protect us against this disease as the virus continues to evolve.”

The boosters until this point have offered protection against severe illness and death against Omicron, but not so much infection.

Data from the Government showed a booster shot was 95 per cent effective against Omicron death.

But against infection, effectiveness was 63-70 per cent, and significantly less after only two doses.

Fortunately, studies have suggested that Omicron itself is a more mild strain and people have suffered more cold-like illness when infected.

Professor Sir Munir Pirmohamed said that the Commission on Human Medicines, which he chairs, “independently reviewed the data on safety, quality and effectiveness and agrees with the MHRA’s decision”.

“The virus, SARS-CoV-2, is continually evolving in order to evade the immunity provided by vaccines,” he said.

“This novel bivalent vaccine represents the next step in the development of vaccines to combat the virus, with its ability to lead to a broader immune response than the original vaccine.”

Stéphane Bancel, CEO of Moderna, said: “We are delighted with the MHRA’s authorisation of our next-generation Covid-19 vaccine.

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“This further highlights the dedication and leadership of the UK public health authorities in helping to end the Covid-19 pandemic.

“This bivalent vaccine has an important role to play in protecting people in the UK from Covid-19 as we enter the winter months.”