A New Generation of Covid Vaccines Is Coming, Some With No Needles, some are nasal spray

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 STAGE

Preclinical Phase I Phase II Phase III Approved

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 STAGE

Preclinical Phase I Phase II Phase III Approved

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 STAGE

Preclinical Phase I Phase II Phase III Approved

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 STAGE

Preclinical Phase I Phase II Phase III Approved

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 STAGE

Preclinical Phase I Phase II Phase III Approved

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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 vaccines