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Scripps Research Spin-Off Ushers a “New Era” in Vaccinology With Platform Technology

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Scripps Research Spin-Off Ushers a "New Era" in Vaccinology With Platform Technology

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Scripps Research spin-off company Ufovax employs the single-component self-assembling protein nanoparticle (1c-SApNP®) platform technology, that was created in the laboratory of Professor Jiang Zhu, to address some of the key challenges in modern vaccine development.

The COVID-19 global pandemic has further emphasized the need for efficient vaccine design, testing and large-scale manufacturing. Ufovax’s “plug-and-play” vaccine platform offers to “streamline” the development process and has already delivered vaccine candidates for global health challenges such as HIV, Ebola and MERS-CoV. Now the company is pursuing a preventive vaccine for SARS-CoV-2, the coronavirus responsible for COVID-19. An initial evaluation of more than 50 designs has led to five candidates that have been validated in preclinical models.

Technology Networks spoke with Dr Colette F Saccomanno, senior vice president of corporate affairs at Ufovax to learn how the platform works and enables low-cost vaccine manufacturing that is readily scalable.

Molly Campbell (MC): For our readers that are unfamiliar the with the company, please can you tell us about Ufovax?

Colette F Saccomanno (CFS):
Ufovax is vaccine company and spin-off from Scripps Research (La Jolla). With advanced approaches to bio-manufacturing, nanotechnology and the rational design of vaccines that optimize antigens via small but critical stabilizing mutations, Ufovax is ushering in a new era in vaccinology and will offer safe and effective solutions that the myriad of vaccines currently available – or under development – do not.

The company holds exclusive Intellectual property rights to certain vaccine work of a team led by Associate
Professor Jiang Zhu, PhD, who holds appointments in the departments of Integrative Structural & Computational Biology and Immunology and Microbiology at Scripps Research.

Ufovax is commercializing a modular, plug-and-play vaccine platform capable of targeting some of the most challenging infectious diseases such as HIV, HCV, RSV, Ebola, MERS, SARS-CoV-1, and now SARS-CoV-2. These are recombinant protein-on-protein-nanoparticle vaccines designed to optimize antigen presentation, simplify manufacturing and maximize a safe and protective immune response for broad use in humans.

MC: How was the 1c-SApNP® vaccine platform technology developed, and how does it work?

CFS:
Dubbed the “single-component-self-assembling protein nanoparticle” (1c-SApNP®), the Ufovax platform makes vaccine development as straightforward as a socket wrench and transforms biological complexity to elegant simplicity.

First, we design the “socket”, an optimal antigen structure, which – for viruses utilizing the class-I fusion mechanism – is called the “Uncleaved, pre-Fusion, Optimized Antigen” (“UFOAg”). Second, the UFOAg is genetically fused to the “handle” which is a multilayered nanoparticle unit that encodes a nanoparticle-forming component, a nanoparticle-stabilizing component and, if necessary, one or more immunomodulators. Third, we bio-manufacture to scale via transient or stable expression in GMP cell lines followed by a robust two-step purification process, combining immunoaffinity and size-exclusion chromatography methods (or other size-based separation methods used in the GMP setting).

The 1c-SApNP platform technology is the result of nearly a decade of research and development work conducted by the team led by Zhu. With expertise in rational vaccine design and antibody discovery, the group has been working to perfect structure-based antigen design and nanoparticle engineering. Combining single-cell analysis and library display with next-generation sequencing, they also work to discover and produce functional antibodies as potential therapeutics, or as core components of immunoaffinity methods that enable a highly efficient purification process for vaccine manufacturing. Ufovax now has a strong pipeline of vaccines that show promise against a wide array of viral and non-viral infectious agents.

Trained as a biophysicist, Zhu has applied a unique set of skills and experience in the fields of physics, biochemistry, virology, immunology, and molecular modeling to “see through” the very complicated three-dimensional structures of antigen complexes, both before and after infection. Understanding, at the molecular level how each virus infects humans allows rational design of “virus-like particles” (VLPs) with optimal shape, size, and antigen display. Such VLP-type vaccines can, in principle, induce a rapid and long-lasting immune response to protect against infection.

MC: What production advantages over the traditional virus like particle (VLP) platform does 1c-SApNP have? 

CFS: First, the Ufovax nanoparticles are pure protein nanoparticles with a well-defined structure. Since the geometry is mathematically defined, there is no ambiguity in its structure and antigen display can be accurately designed and modeled on a computer. Since there is no lipid involved, the manufacturing process is easy and robust. Second, while both traditional and 1c-SApNP VLPs are self-assembling, traditional VLP assembly is a delicate and sometimes multiple-step process that is susceptible to many factors, whereas 1c-SApNP VLP assembly is a fast, single-step reaction. As a result, the materials produced are cleaner and the polishing process is easier. Third, since 1c-SApNPs often have exposed N- and C-termini on the surface, it is possible to genetically fuse a large antigen (e.g., HIV-1 and coronavirus spike proteins) to a 1c-SApNP subunit and the fusion construct will still express and self-assemble. This would be very difficult, if not impossible, for VLPs derived from virus shells. Finally, SApNPs of bacterial origin are robust proteins tolerant of mutations and insertions, allowing further protein design and engineering to optimize their function as antigen carriers (on the 1c-SApNP surface) or as cargo for immune modulators (inside the 1c-SApNP shell).

Perhaps the single, stand-out differentiator of the Ufovax 1c-SApNP production process is the “one-for-all” bioprocess that works the same way for all vaccine products. For any given vaccine candidate, a single plasmid that encodes ALL structural/functional components of the vaccine is transfected into the same widely-used GMP CHO cell expression system and forms the desired nanoparticle vaccine product through self-assembly. These nanoparticle vaccines resemble the target both morphologically and antigenically but lack any infectious capacity.

MC: How is 1c-SApNP optimized for low-cost, large-scale industrial manufacturing? Why might this be advantageous in the context of the COVID-19 global pandemic?

CFS:
The Ufovax 1c-SApNP is the best-in-class platform technology for protein nanoparticle vaccines. The optimal construct design coupled with the robust expression/purification system enables both high yield and high purity. As a platform, this makes Ufovax vaccine manufacturing low-cost and readily scalable. Moreover, the fully assembled 1c-SApNP vaccine is thermostable, which facilitates distribution and minimizes supply chain concerns. In contrast, most viral vector vaccines would require “cold-chain” storage and distribution. This is especially important in the context of any global pandemic, not just COVID-19.

MC: Please can you discuss the company’s creation of a vaccine against SARS-CoV-2? How does the vaccine work and at what stage of preclinical testing is the vaccine currently? 

CFS: Zhu has been conducting vaccine research for more than ten years, including his time at the National Institutes of Health (NIH) Vaccine Research Center. Prior to the emergence of the COVID-19 pandemic, he had been a co-Investigator on two NIH-sponsored vaccine programs for coronaviruses, specifically SARS (now SARS-CoV-1) and MERS and the rapid development of our COVID-19 candidate(s) was enabled by this foundational understanding of coronaviruses.

Against this backdrop, the 1c-SApNP approach was proven to be a bona-fide plug-and-play platform technology. Our first COVID-19 candidate was purified on February 28, 2020. Further evaluation of 150 constructs led us to five final candidates and our pre-clinical mouse immunogenicity study was initiated in late May.

The serological analysis of over 80 samples was recently completed and represents one of the first examples of a “systematic” rational design and preclinical study for COVID-19 vaccine development. Our mouse data demonstrate high titers of neutralizing antibodies and is consistent with the expectation of a single- or two-dose regimen. A publication is in preparation.

The Ufovax COVID-19 1c-SApNP vaccine is a spike-based vaccine but with a twist – one that locks the spike in its pre-fusion state and presents 20 such spikes per nanoparticle. A very potent immune response is thereby elicited. In fact, the Ufovax design “predicted” and accounted for the pre- to post-fusion conformational changes that were recently reported in
Science (Y. Cai et al., Science 10.1126/science.abd4251 (2020). Our patent application covering vaccine design strategies for all three coronaviruses was filed on June 29th.

MC: Can you discuss the portfolio of 1c-SApNP vaccines candidates that have been developed thus far?

CFS: As a spin-off of Scripps Research, the Ufovax pipeline has a strong and distinguished pedigree. Built on the history of all the work and attempts to create an effective vaccine against one of the most challenging global health crisis in recent history, Ufovax began with the intention of advancing its HIV-1 vaccine. With the Company’s strategic plan based on the most impactful infectious diseases, we then moved on to HCV, RSV, SARS/MERS, Malaria and Ebola, until the world was interrupted by COVID-19 and nearly all attention shifted.

Despite having to address the COVID-19 pandemic, Ufovax is still on-track with other programs, including HIV-1 which was selected by DAIDS/NIH to be included in the NIH’s clinical trial currently scheduled to begin in 2022, and RSV and HCV, with those clinical trials targeted to begin in Q4 2021. We have filed six patent applications covering HIV, HCV, RSV, and the coronaviruses; two of which have been allowed by the USPTO. Our patent on the Ebola vaccine is being prepared for filing in August 2020.

MC: What are your plans for progressing the vaccine against SARS-CoV-2?

CFS:
Ufovax is negotiating with several potential partners for SARS-CoV-2 vaccine development. Our plans include completing the ongoing mouse immunogenicity study, conducting GLP-toxicology studies, and filing an IND application in Q4 2020 to enable first-in-human studies by the end of 2020 or in early 2021.

MC: What are the biggest challenges when developing vaccines?

CFS: For scientists pursuing rational vaccine design, the biggest challenge lies in how to present the relevant and correct antigen conformation to the immune system and thereby induce a robust and long-lasting immune response to prevent virus infection. The success of rational design relies, in large part, on the in-depth understanding of the virus fusion mechanism, whereby the virus surface glycoprotein complex undergoes a dramatic conformational change. This change enables the physical contact of the cell and virus membranes and the creation of a fusion pore that allows viral entry into the cell. Many viruses threatening humanity such as HIV-1, Ebola, Flu, RSV, and SARS-CoV-2 use the class-I fusion mechanism, which renders their surface glycoproteins unstable in the pre-fusion conformation. Through evolution, these viruses have also acquired various molecular trickeries to evade immune response by exposing immunodominant epitopes on the unstable glycoproteins or producing numerous “decoys” so that the antibodies generated against these targets are ineffective at blocking the virus entry. Therefore, the biggest challenge in vaccine development for this large family of viruses is to “rationally redesign” their surface glycoproteins to stabilize them in the prefusion state and to present them to the immune system either as a vaccine antigen, or more effectively, on a large virus-mimicking nanoparticle to elicit a strong immune response.

MC: How has the COVID-19 global pandemic impacted vaccine design, testing and manufacturing?

CFS:
Long feared and even publicly attacked as doing more harm than good, the value of vaccines is now globally acknowledged. The COVID-19 global pandemic has elevated the urgency for vaccine development to an all-time high. Despite unprecedented funding, there has been little or no impact on the design of vaccines as a result of COVID-19.

The majority of current COVID-19 vaccine designs are largely based on approaches that have not yet produced commercial vaccine products. All “major players” working on COVID-19 are using the wildtype spike S protein as antigen with/without proline capping.  As the aforementioned Science article pointed out, the wildtype spike is unstable and proline capping, as a spike-stabilizing strategy, it is not as effective as previously thought. Such suboptimal antigen designs may lead to a dampened immune response and potentially introduce safety concerns due to the presence of post-fusion or misfolded spikes in these vaccines.

The Ufovax design invokes its UFOAg with patented mutations to eliminate the post-fusion conformation of the spike protein. This confers a higher degree of spike homogeneity, has already demonstrated greater immunogenicity in our mouse study, and suggests fewer safety concerns for future use in humans.

Vaccine manufacturing is often complicated and tedious, posing significant challenges for large-scale production in the time of a pandemic. The field is seeking an easy, fast, scalable, and cost-effective manufacturing process that can be standardized and applied to a wide range of vaccine products. Ufovax’s 1c-SApNP platform technology offers an elegant and workable solution.

Lastly, the testing of vaccines may finally come into the 21st century as a result of the global reaction to the COVID-19 pandemic. Having a vaccine platform means not having to “re-invent the wheel” every time a new vaccine is needed. With the Ufovax 1c-SApNP approach, much of the safety is “built-in” from the start. Removing regulatory hurdles and getting new vaccines developed more rapidly means that appropriate human trial populations will exist for proper cohort assembly. The Ufovax 1c-SApNP platform is the modular plug-and-play solution.

Colette F Saccomanno CFS was speaking to Molly Campbell, Science Writer for Technology Networks.

Fashion

Fashion Briefing: Fashion’s emerging founder-investors are mega-influencers – Glossy

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Fashion Briefing: Fashion’s emerging founder-investors are mega-influencers – Glossy

Fashion’s OG Instagrammers are building empires and, at the same time, growing their influence beyond the industry.

After being schooled for years on the workings of the fashion industry, mega-influencers including Danielle Bernstein (2.7 million Instagram followers) and Rocky Barnes (2.5 million Instagram followers) are graduating to careers less reliant on brands. To take it to the next level, they’re leveraging their prowess and communities, driving deals with effective business partners, and evolving their focus, based on the industry’s direction and their own passions. The emerging results, for both Bernstein and Barnes, are personally-backed brands and investment portfolios set to expand based on early successes.

“The plan is to grow, in a big way,” said Bernstein. “I’m a serial entrepreneur, so I’ll always want to introduce new businesses and categories to my brand. And I’m angel investing and joining the board of advisors for so many companies. That’s the future of the creator economy: harnessing and creating community around your existing followers and then figuring out how to monetize that.”

In 2019, upon inking a licensing deal with New York-based clothing company Onia, Bernstein launched the Shop We Wore What e-commerce site, populated with her expanding We Wore What fashion collection. The collection has been at the center of much recent controversy, due to allegedly including copycat designs. According to Bernstein, she turns to vintage pieces, editorials and travel for inspiration. Bernstein’s also become an investor and advisor for hair supplement company Wellbel and CBD brand Highline Wellness. In May, she became active on Patreon, offering exclusive video content to paying members of her community.

In addition, Bernstein heads up We Gave What, a charitable arm of her company. In 2019, she launched tech company Moe Assist with a project management tool for influencers, though its social accounts have been inactive for two-plus months. When asked for comment, a spokesperson said Moe Assist is in a new fundraising stage and “should have news to share shortly.”

Barnes, meanwhile, partnered with Reunited Clothing to come out with her apparel company, The Bright Side, in December. And she recently became a first-time investor-advisor, for 6-month-old SMS shopping platform Qatch. She announced the partnership in an Instagram post on Monday.

“I feel like a grown-up,” she told me, before confirming that she’s interested in investing in more companies. “Diversifying my business has been a really big [focus] for me. I interact with so many different brands and companies on a daily basis. Using my market knowledge in ways that can help other people is fulfilling and exciting for me. And I especially love when I can be involved with a company from the beginning.”

Building on their content creator role in fashion is a natural progression, both said. And it plays into many industry shifts: On its way out is fashion’s DTC era, largely fueled by Harvard Business School and Wharton graduates using a plug-and-play, marketing-heavy business model to launch brands. More consumers are prioritizing quality, differentiated products, making industry experience and style expertise greater virtues among insiders. At the same time, consumers are increasingly taking shopping cues from relatable, platform-native celebrities, moving on from authoritative editors and more closed-off celebrities.

The school of collaborations
The collaborator-to-founder shift isn’t the newest thing. Other longtime influencers that have made the pivot include Arielle Charnas, with Something Navy; Aimee Song, with Song of Style; Rumi Neely, with Are You Am I; the list goes on. Most often, the names behind these brands don’t have formal design and business training — for her part, Bernstein said she “went to FIT for two years, but didn’t study design and production.” But, for years, they’ve worked hand-in-hand with companies to bring their visions to life. And along the way, they’ve come to know what resonates best with their vast communities, from marketing to merchandising to product.

“My most successful collaborations have led to the largest share of my business,” said Bernstein.

Bernstein’s partnership with Onia came out of her swimwear collaboration with its Onia brand, in May 2019. On the collab’s launch day, it drove $2 million in sales, and an included style was the brand’s best-selling swimsuit of the summer. Also in 2019, Bernstein collaborated with Joe’s Jeans on multiple denim collections. The launch day of the first, in March 2019, marked Joe Jeans’ best sales day to date, said Jennifer Hawkins, the brand’s svp of marketing and innovation on a Glossy Podcast in October.

Both served as learning opportunities for Bernstein, who said — as with all of her collaborations — she took full advantage: “It was never just [uploading] a post, and then I went away,” she said. “I always wanted to know how the performance was, in terms of sales, and asked questions: ‘Can you share the analytics?’ ‘What did you see on your end?’ ‘What worked and what didn’t work?’”

She added, “They provided a ton of data, in terms of what I could sell and what the market was missing.”

Likewise, she said, she always followed and shared with partner brands the Instagram Insights and Google Analytics numbers around her corresponding posts. Doing so gave all parties a 360-degree view of a collaboration’s success.

“I’ve learned what works for brands so they get the largest return on their investment,” she said.

For example, she’s learned to lean on her audience’s tastes, versus rely on her own, by allowing them to offer feedback throughout the design process through Instagram. That’s included the selection of fabrics and colors and the fit sessions with models. She only spotlights her favorite styles and what she wears in her own social posts, as a play for authenticity.

According to Bernstein, the collaborations with brands allowing her to play an advisor role — by guiding them on influencer partnerships, marketing and messaging — are always more successful. And they often turn into longer-term investment or advising partnerships.

Bernstein chose to work with Onia on the We Wore What collection based on its prioritization of quality and fit, and ability to keep to affordable retail prices. Currently, prices on the We Wore What site range from $20, for a scrunchie, to $228, for a vegan leather jumpsuit.

Barnes was also ready to go out on her own after finding the right partners. Her Reunited Clothing partnership came after working with the company to create her Express product collaboration, in early 2019. On its first-quarter 2019 earnings call, interim CEO Matthew C. Moullering said the company had seen “a strong start to [the] collection both in-stores and online and [believed] it [was] helping to introduce the brand to a new audience.”

“Having your own brand is terrifying,” Barnes said. “But I like that I’m in control and not so dependent on doing the day-to-day posts promoting other companies.”

But, she added, “One of the huge benefits of working with all these different brands on all these different projects is that we’re constantly getting introduced to new people and seeing who we like working with.”

Barnes’ internal team consists of her husband, who’s the “business brains” of the company, she said, and an assistant.

Like Bernstein, Barnes stressed the need for outside support in the production process: “I love such quirky, crazy things, but I also understand what is realistic for a buyer and a normal girl buying clothes,” she said. “The experience of taking ideas and making them work for a bigger group of people was my learning curve going into a business. It’s important to have a good, diverse team around you who can make your idea something that’s marketable.”

For its part, We Wore What has seen “200x growth in the last year,” as it’s expanded to new categories, Bernstein said. Its ready-to-wear, swimwear, resort wear, and activewear are now sold in “dozens and dozens of retailers around the world,” many of which offer style exclusives; they include Revolve, Bloomingdale’s and Intermix.

“Launching my own brand was putting the proof in the pudding for the power of influencers, when it comes to selling product,” she said.

As with her Joe’s and Onia collaborations, Bernstein sees a rush-to-buy with We Wore What product drops. “The first 10 minutes is when we see the biggest portion of our sales for the entire collection,” she said.

To build buzz, Shop We Wore What’s Instagram account (213,000 followers) features in its Stories the line sheets of the soon-to-launch styles, allowing customers to thoughtfully plan their buy. Doing so has led to lower return rates, Bernstein said. The company’s marketing mix also includes text messages and emails, VIP discounts and user-generated content.

Bernstein has a staff of four people, which include a chief operating officer and a brand coordinator. She said she prioritizes establishing partners with skills and expertise she doesn’t have, so she can learn from them along the way. Ideally, she’d have learned about tech packs, fittings and production logistics in school, but she’s training as she goes.

Moving forward, Bernstein said she plans to extend the size range of We What What styles, which are currently available in sizes XS-XXL, and launch collections with collaborators to sell exclusively on her brand’s DTC site. In addition, she aims to eventually open “experimental” physical retail, starting with pop-ups.

As for her investment-advisor portfolio, she’s currently in talks with companies centered on the concepts of “being able to sell your closet and even rent your closet.”

As for Barnes’ Bright Side, she said it will hit “a bunch of new retailers this year.”

Moving beyond fashion
Up next for Shop We Wore What is a new product category that will hit before the holiday season. Considering her passion for home furnishings and decor — based on her @homeworewhat Instagram account (7,500 followers) and recent press coverage of her new SoHo loft — it’s a safe bet that a home-related category is in the cards.

Likewise, Barnes hinted at a future Bright Side home collection, following her recent, two-year home remodel, which she’s getting set to debut on social media.

Lifestyle brands are the clear goal.

“I would love to be a combination of Rachel Zoe and Martha Stewart, just having my hands in everything and creating this really beautiful lifestyle where you can entertain and be fashionable,” Barnes said. “That’s kind of the dream.”

She added, “Fashion is where my heart has always been, but I’m growing as a person and there’s so much more in my life right now: my family, my home — and I’m getting older, so beauty [and skin care] makes sense now. Sharing all of that with everyone seems so natural; it would be weird if I only did fashion.”

As for future investments, though Quatch fits perfectly into Barnes’ world, with its fashion-tech focus, she said she’s open to investing in any company where she sees opportunity.

What’s more, she has no plans to retire from social media, though she has yet to tackle TikTok.

“People’s need for content has only increased, so I’m posting and creating content more than ever,” Barnes said. “But I’ve learned to become more of a hard-ass with brands. The companies that are willing to work with me and [facilitate] the most like authentic relationship possible are the ones I move forward with.” Reunited can attest.

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South African bowler Tabraiz Shamsi: Amateur magician; professional tweaker-trickster

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Harry Potter fans would know this as the Room of Requirement; muggle cricketers dub it backend operations. Tabraiz Shamsi is an amateur magician. He is also a professional worrier of why some googlies don’t turn as much as he’d want, in cricket.

For the Proteas chinaman bowler, the room of requirement from where he could pull out any game data, used to be the dependable ‘P Dawgg’, former South Africa analyst Prasanna Agoram combining his ken and nous and fast processing laptop. Prasanna enviably would be privy to the trial (and error) runs of Magician Shamsi’s classical Tourniquet coin-drops with the cricket ball. Which was the unglamorous, quirk-in-progress of his left-arm leg spin.

At the stroke of 1 a.m, oftener than not, Shamsi would come looking for what he called ‘shit balls’, in what Prasanna reckoned were otherwise impressive, less-than-run-a-ball bowling spells. This was that one specific delivery that went for a six to sully Shamsi’s 4-0-22-3 T20 match figures. It was the bugs, not the features, that the 29-year-old would cussedly fixate on.

“I’d never point out that he’s missing his length or the back foot was collapsing, at 12.30 in the night. Because Shamo, you see, would then take me to the nets at 1 a.m! He’s capable of calling the manager and telling him at that hour that I have to practice NOW. You had to be careful about what you told him at 1 a.m,” Prasanna laughs, underlining ungrudging admiration for the Proteas spinner’s dedication.

A series of self-recriminations in staccato would follow the ‘Bhai, can you please put on the shit-ball that went for a six.’ “He’d curse himself watching replays: ‘no good, not international class, garbage ball.’ If you try telling him it is ‘well-played’ from Jos Butler and not exactly a poor ball, he’d be hard on himself and say, ‘This is nonsense from Shamo’,” Prasanna recalls of his exacting standards.

For, the South African World No 1 spinner – who lends mystery to the Saffer bowling attack if not entirely upstaging their thunderbolt battery of pacers – knows that all sleights of hand, can come with uncontrollable twists of fate. Both in magic, and cricket.

A young boy of 15 at Paarl who tried to bowl quick like Wasim Akram and Chaminda Vaas, had wound up as a left arm leg spin all-sorts, after years of compulsive fine-tuning. And taken failures and omissions into his run-up’s five-strides.

***
Born in Johannesburg, Shamsi wanted to be a super quick in the land of bolting pacers. His progress though didn’t follow the regular route of being identified early for First teams at schools and playing age-groups. Also, he was told he wasn’t quick enough.

Speaking to the podcast ‘Pavilion conversations with C.S’ recently, Shamsi recalls his earliest break at age 15, bowling alone in the school nets, with the cricket coach’s office nearby. The coach would stop by and ask him what he was upto. “I said, ‘Sir, the U15 trials are coming up. I want to make the Paarl team wanna progress’. He told me – you are not gonna make it. But even there I thought he realised the type of character I am. That was just his way to push me even harder. He said ‘Don’t waste your time practicing coz you won’t get selected. And i was even more driven,” he told the host Mr. Chiwanza.

Shamsi would end up with most wickets that tournament, make the B team (“Still not A”), followed by U17 and U19s for the local side. “I didn’t get selected for SA U19s or invited to camps. My past was little different. In fact I got my opportunity at semi-pro cricket because one player got selected for U19s and went to the World Cup. A spot opened up because of him. I just knew that was my chance I had to make it work. And fortunately I performed. When he came back from the World Cup, he couldn’t get into the team,” Shamsi recalled.

It was around 2015-6 after he had zeroed in on Chinaman as his chosen bag of assorted tricks in franchise, provincial cricket, that he first sought out Prasanna, while closely following senior leggie and his ‘bruv’ Imran Tahir. Prasanna promised to compile a list of outstanding T20 spinners of that year for comparison, when Shamsi asked him: ‘Why just T20? I want to play all formats.’

Prasanna promised to revert after two days on Friday, and on Monday, he had a message from the hotel lobby at 10.30 am that Shamsi was waiting. “Normally, cricketers will turn up at 11.30, if the analyst time is 10.30. This guy made me abandon my breakfast and was ready with a list of questions. I’d prepared a presentation earlier on bowlers like Warne, Ajmal and Herath and how they bowled on unhelpful tracks, what lengths to bowl at what stage, and offered to email it to him. He tells me: “No. I’ll write it down in my own words. I don’t want shortcuts.”

Shamsi would sit and plan for every batsman – his notes diary in tow, even on matchdays when he wasn’t in Playing XI. And once he would spill the beans on why brainwaves struck him at 1 a.m – his preferred time to brainstorm with the analyst. “He once told me he eats my brain at that hour, so that he gets dreams of how to get a Kohli or Sharma out, so he can wake up next day he can execute the training plans.”

Once he came angsty about his googlies not spinning as much as Kuldeep Yadav or Brad Hogg. “When he said it’s not spinning, I told him Shamo’ you didn’t bowl any googly. That’s it. He hit the nets and bowled 1000 googlies non-stop and then said, he’s now hitting the groove.”

But nothing had prepared Prasanna for Shamsi’s mic-drop in the pink ball Test against Australia where the Chinaman was fancied as it’s tougher to spot the wrist in the Adelaidian twilight. Shamsi was instructed to block for 20 balls and support Faf as Proteas were hanging on at 210-9. Shamsi would announce he would score a 50 – against Pat Cummins, Hazlewood and Starc. Finally he was unbeaten on 18. “He came back and blustered ‘If someone had suported me, I’d have hit that 50’.”

***

This constant state of ‘upbeat’ – talking up his own abilities to score a 50 coming at No 11 against Cummins & Starc – might well be the sort of swag and sizzle that the staid South African teams need at ICC tournaments. For a large part of the last 30 years, the Proteas have entered tournaments with burdensome tags of ‘talented’ and ‘favourites’ and come up short. The tasteless mocking glee of choke-jokes has run its course, and being light-weights might well prove liberating.

For all their botched run chases in 50 overs, South Africa can stake claim to the historic highest run-rally to 438. And the innings-interval remark of Jacques Kallis, the most expensive bowler in Australia’s 434, who had quipped “Guys, I think we’ve done a good job. They’re 15 runs short.”

Shamsi likes his boisterous one-liners too. And his showboating and noisy over-the-top pantomime aggression.

After starring in a T20 win against Ireland earlier, he would tell South African journalist Telford Vice, “In my young age, I started as a seamer but was told I’m not quick enough to be a fast bowler so became a spinner. Grew up watching Andre Nel, Dayle Steyn, Allan Donald, that’s where aggression comes from.”

He knows it’s a double-edged sword and a bowler can be packed off, but it can disrupt batters too. “Whatever it takes to win. I’m in charge of making our presence felt on the ground and ensure the team never backs down from opponents,” he added.

Shamsi recently responded to Darren Sammy’s tweet on who would win the T20 World: “Come on skipper, you know the answer to this already…. South Africa of course.” Scroll down the thread, and some mocker mangles his grammar: “are you comedy me”. A good laugh was had by all. Pressure punctured.

“He’ll say things like ‘I’ll single-handedly win this,” Prasanna says, “Whether it happens or not, it gives confidence to people close to you – your team.”

***

Shamsi’s made it to the top of rankings, taking 49 wickets from 42 T20Is, at a strike-rate of 14.8 and averaging 6.6. There’s been a bucketful of wickets in franchise cricket and The Hundred. He’s 31 and has bidden his time to make it to the national team, and another 4 years into the Playing XI. The Wicket then, is an ocassion to celebrate, he reckons.

“I’m a human being and not a robot and want to make long-lasting happy memories that will live with me forever long after my career is done and that is the reason behind my celebrations,” he wrote in a social media post once. “My celebrations mean no disrespect to the opponents. They help me enjoy myself, switch on and off during the game to release some pressure, and put some smiles on people’s faces too.”

There’s the “Shoe” that got going in the West Indies, where within seconds of a wicket, he’d shrug his ankle open from the left shoe and pretend to speak on a landline receiver. Then there’s the bus driver-celebration with Carlos Braithwaite and something about a birdie’s chirp. A flying kiss to the wife and a mock punch to a fielder like a streets hip hopper. Though the untold back-stories raise anticipation of what he’ll whip up next.

Prasanna says there can be new hairdos before every game, sometimes “thrice a week”, and that magic tricks and celebrations are practiced as diligently as the googlies and top-spinners. “Not only will he say, ‘Tomorrow I’ll get Ben Stokes out.’ He’ll also ask you to watch the celebration.”

Amongst his most famous on-field triumph-trumpetings after snaring a batter is pulling a wand out of a hankey – a magician’s staple. But never in cricket, where magic’s glossary is slathered on the slow bowlers and their guiles.

T20 commentators love his name, lending it a South American football match caller’s vroom: “Shaaa-mzzziii”. But it’s the celebrations that can befuddle the most trained of raconteurs. When Shamsi got Wihan Lubbe in the Mzansi Super League, the commentator would build up to the expected celebration. “Is the shoe coming off? No. Look at that…it’s magic,” he would chortle. Cricket was momentarily put to the side, before he resumed confused: “That was a legspinner…… Beg your pardon… Offspinner… That did the trick..” Shamsi’s delivery had jagged away from the leftie and the post-celebration left the commentator’s mind in knots.

Appearing on the Dan Nicholl Show in SA, Shamsi had pulled one of those ‘I can guess the card pulled out of the deck after being shuffled’ tricks. It was ace of spades.

Magic had been his fallback option till age 16, he’d say. “So if cricket doesn’t work out… I ll practice magic for 10 years… But naa… It’s gonna work out.. I’ll bamboozle you all,” he would say, charming the audience.

At the start of the magic gig, Shamsi had handed a sealed envelope to the host. “Sealed with Proteas saliva” Nicholl had joked with whispered reverence. The distracting envelope had briefly become the centrepiece, and Shamsi would explain later:
“You satisfied you made me stop shuffling when u wanted me to? Funny thing is…You thought you were in charge of the trick… Telling me when to stop. Even though it’s your show, I’m running this party… I was controlling you and I actually made you stop at a specific point. …And to prove that I had written down something in this envelope before starting the trick..” It read Ace of Spades.

Shamsi’s assortment of Chinaman, is a bit like that: planned spontaneity. Allan Donald in a video while introducing him to RCB few seasons ago, said: “Left arm, tweaks it this way, tweaks it that way, then tweaks it the other way.” Offering attacking options in the middle overs, with his ability to turn ball both ways, and variations of top spinner, the side spinner and googly, makes him effective against both lefties and righties. The constant explosion of activity – before, right after when appealing (he once did a spot of bhangra jumps, then sat down altogether while pleading a decision) and when celebrating, is in fact the sealed envelope distraction.

Yet, bad days are not unfamiliar to Shamsi, and his role can be flexible like the magician’s wand, like in the West Indies, to keep things quiet, contain against the big power hitters. “There’s two ways to skin a cat… Not really fussed about not getting wickets in WI. That was a different role,” he told the media later.

Sometimes the magic is in not believing the flimflam and sleight. Like rankings. “I don’t lose sleep over being No 1. Obviously it’s a nice feeling to be on top. But I’ve said it before and I truly mean it. I don’t even think I’m the best bowler in our team. We have some great bowlers in the unit. Rankings don’t mean anything if a batsman gets hold of you. I don’t even know how those rankings work honestly.”

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Five great Twenty20 World Cup upsets

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