By Michelle Fay Cortez Dong Lyu│ Bloomberg│6 min

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The coronavirus outbreak made household names of companies like Moderna Inc. and BioNTech SE, whose shots offered hope for ending the pandemic. Now a new wave of vaccines is on the horizon that may get the world over the finish line of inoculation.

Protecting 7.7 billion people is a herculean task. There are more than 250 vaccine candidates in the wings to take on the challenge, including 82 in human studies. In addition to sheer numbers, they offer unique benefits compared to the dozen now available.

The next generation includes shots built from the coronavirus’s genetic material and nasal sprays that defend without using a needle at all. They are stealthy, faster to make and easier to ship, offering workarounds for hurdles that limit the impact of the first inoculations to reach the market.

“It’s absolutely essential to share vaccine products with the entire world as quickly as possible,” said Richard Hatchett, chief executive officer of the Coalition for Epidemic Preparedness Innovations, which accelerates development of vaccines, including those against Covid-19. “The virus will have less opportunity to evolve, and it will slow down the rates of mutation that we’re seeing.”

Here’s what you need to know about the next wave of vaccines:

One-Shot Wonders

With most Covid vaccines requiring two shots, those that need only one will simplify the process. This approach is known as viral vector technology. It uses an unrelated virus, one that’s been modified so it doesn’t cause infection, to insert the directions for making the coronavirus’ spike protein into healthy cells. Those cells then crank out large amounts of the spike protein, triggering an immune response. Of the dozen candidates in human studies, most involve one injection.Pros

• With one shot, they’re faster and stronger—though boosters may be needed
• May be easier to update for new strains, since different genetic sequences can be delivered via the same viral vector
• Can be kept refrigerated for up to two years.

Cons

• People can be immune to the vector, which is often an adenovirus – a frequent cause of the common cold
• All that spike protein production can trigger an immune response that can result in stronger side effects

Current use in other vaccines

• Ebola vaccines use viral vector technology; scientists are evaluating it against Zika, influenza and HIV.

Companies involved

• CanSino Biologics Inc, Johnson & Johnson, Gamaleya Research Institute/Russia’s Health Ministry

Current stagePreclinicalPhase IPhase IIPhase IIIApproved

Response Trigger

The most common type of vaccine now in human trials—accounting for nearly one-third of those in development—protein subunit shots use a fragment of the virus to generate an immune response. It’s usually the famed spike protein that dots the surface of the coronavirus, combined with a chemical known as an adjuvant to deepen the reaction.Pros

• A mature technology that makes a stable shot
• No risk of infection because they don’t use live virus
• Easier and less expensive to manufacture, with plenty of capacity already in the system

Cons

• Finding the right protein segment can take time
• The immune system may not recognize the protein fragments as a serious threat, and generate a weaker response
• Booster shots may be necessary
• Production of adjuvants has slowed due to bottlenecks amid surging demand

Current use in other vaccines

• Subunit vaccines are used to prevent hepatitis B, whopping cough and pneumococcal pneumonia

Companies involved

• Novavax Inc., Anhui Zhifei Longcom Biopharmaceutical/Chinese Academy of Sciences, Clover Biopharmaceuticals Inc./GSK/Dynavax, COVAXX/United Biomedical Inc.

Current stagePreclinicalPhase IPhase IIPhase IIIApproved

Virus Decoy

These vaccines contain a coronavirus decoy—a protein shell whose shape closely mimics the virus without any of its genetic material. The so-called virus-like particle is still able to generate an immune response against the real thing.Pros

• They have the structure and form of the virus to stimulate a strong immune response without any risk of infection
• Safe for people with weakened immune responses
• Potentially be better at dealing with mutations

Cons

• It’s difficult to make high quality, stable decoy particles in large quantities
• Manufacturing costs are high
• The origin and composition of the outside of the Covid virus is complex, making mimicry difficult

Current use in other vaccines

• This approach is used to prevent cancer-causing human papillomavirus (HPV) infection, hepatitis B and malaria

Companies involved

• Medicago Inc., VBI Vaccines Inc., Serum Institute of India/Accelagen Pty/SpyBiotech

Current stagePreclinicalPhase IPhase IIPhase IIIApproved

DNA Building Block

Like the breakthrough mRNA vaccines from Pfizer Inc., BioNTech and Moderna, DNA vaccines insert a bit of genetic code into a human cell. The cell becomes a factory, producing the coronavirus spike protein to elicit an immune response. The DNA vaccines have to take an extra step, though. They must convert the genetic material into mRNA, which contains directions for making the proteins. Should a vaccine using this approach get to the market, it would be the first of its kind.Pros

• Can mobilize the immune system to slay virus-infected cells in addition to creating antibodies to prevent a viral attack
• May be cheaper to make than protein-based vaccines and more stable than mRNA shots
• Ideal for people with compromised immune systems.

Cons

• Immune response may be weaker and the vaccine less effective
• Some need to be used with a “gene gun” to push the genetic material into the cells with electric pulses, an additional logistical challenge during mass inoculation efforts

Current use in other vaccines

• None

Companies involved

• Zydus Cadila, AnGes/Takara Bio/Osaka University, Inovio Pharmaceuticals/International Vaccine Institute/Advaccine Biopharmaceutical Co.

Current stagePreclinicalPhase IPhase IIPhase IIIApproved

Nasal Spray

Getting vaccinated doesn’t always require an injection. Some immunizations can be sprayed into the nose, where the virus often first takes hold. Several types, including the viral vector and virus-like particle approaches, can be given as a nasal spray.Pros

• May provide better protection against the virus given it typically infects through the respiratory tract
• Avoids needles
• Easier to administer than shots that require freezing temperatures and preparation by medical staff

Cons

• May cause more severe side effects
• Their use and potency may be limited in certain age groups

Current use in other vaccines

• Nasal sprays are widely used as alternative to flu shots

Companies involved

• Codagenix/Serum Institute of India, Hong Kong University/Xiamen University/Beijing Wantai Biological Pharmacy

Current stagePreclinicalPhase IPhase IIPhase IIIApproved

Coronavirus Medley

SARS-CoV-2 is mutating, and there is concern that the current raft of shots may not provide immunity against those variants. But some vaccines are now simultaneously targeting several strains. There are also combination shots designed to protect against Covid and seasonal influenza. While research is at an early stage, these vaccines could be the ultimate answer to the constantly mutating coronavirus, so regulators may fast-track such shots if they’re modified versions of already-approved vaccinesPros

• Protect against a wide range of viral variants, reducing the hassle of having to vaccinate repeatedly
• Coverage for multiple infections with one shot, reducing the burden on patients and health systems

Cons

• Relatively unproven technology, and it’s still unknown if multivalent shots can be successfully created against coronavirus strains
• Difficult to pinpoint which component could be the cause of any side effects in combination vaccines

Current use in other vaccines

• Influenza vaccines contain multiple strains; childhood vaccines are given in combinations that cover several pathogens

Companies involved

With combination immunizations:

• Novavax Inc., Vaxess Technologies/Medigen Vaccine Biologics, Vivaldi Biosciences

With multivalent vaccine:

• Moderna, Clover Biopharmaceuticals Inc.

Current stagePreclinicalPhase IPhase IIPhase IIIApproved

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