(This is the second part of a special report by SunStar Philippines on efforts to defeat the Covid-19 pandemic through vaccination.)

A VACCINE is a type of medicine that mimics the bacteria or virus that causes a disease, and triggers the creation of antibodies, protecting a person from the actual bacteria or virus.

It saves lives, reduces hospitalizations, and eventually stops transmission of a contagious disease.

Remember smallpox? Probably not, because it was eradicated 40 years ago. Among the infectious diseases that are no longer prevalent because of vaccines are polio, measles, rubella, chicken pox, mumps and diphtheria.

Vaccines against coronavirus disease 2019 (Covid-19) were developed less than a year after the World Health Organization (WHO) declared a pandemic.

They come in multiple technology platforms, demonstrate efficacy at various levels and require different cold chain specifications.

“But the good news is they’re all relatively efficacious at preventing symptomatic Covid-19,” American virologist Angela Rasmussen said in a webinar for journalists on January 29.

“The reason why we need different vaccines, given that they have different efficacy profiles, is because there are going to be different situations in which a given vaccine is going to be more useful than another,” she added.

The efficacy of a vaccine differs from its effectiveness. The Gavi Vaccine Alliance says efficacy is the degree to which a vaccine prevents a disease during clinical trials while effectiveness refers to how well it performs in the real world.

Comparing efficacy rates may be difficult as the methodologies and variables used in clinical trials vary.

Citing the WHO draft vaccine landscape, the Department of Health (DOH) in the Philippines said there are 235 candidate vaccines under development as of January 5. Of these, 63 are under clinical development, including 15 in phase 3 clinical trials and six in phase 2/3 clinical trials.

Under the recently approved national deployment and vaccination plan, 11 vaccines are shortlisted for evaluation by the vaccine expert panel.

The developers of these 11 vaccines are Sinovac, Sinopharm, Bharat Biotech, Anhui Zhifei, Novavax, Clover, Janssen, Gamaleya, AstraZeneca, Pfizer and Moderna.

These candidate vaccines were developed using messenger RNA (mRNA), adenovirus vectors, inactivated virus, and subunit.

mRNA vaccines

Rasmussen said mRNA vaccines teach cells how to make the spike protein of Sars-CoV-2 to trigger an immune response and train the body to fend off an infection.



Examples of mRNA vaccines are those developed by Pfizer Inc. with BioNTech SE of Germany, and by Moderna Therapeutics.

Rasmussen noted that the mRNA vaccines are extremely efficacious at preventing symptomatic Covid-19, but require ultra-cold freezers that are not widely available even in the US, much less in lower middle-income countries.

“Those vaccines are great, but they’re also difficult to deliver and present major distribution challenges,” Rasmussen said.

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Pfizer-BioNTech vaccine (BNT162b2)

Efficacy: 95 percent in the study population and at least 92 percent among all racial groups based on phase 3 clinical trials

Age range: 16 years and older, but not recommended in 80 years and older in Norway

Regimen: 2 doses 21 to 28 days apart

Logistics: Unopened vials must be stored at -80 to -60 degrees Celsius during transport. In hospitals and vaccination centers, these may be stored at 2 to 8 degrees Celsius, but only for five days.

Common side effects: pain, swelling, redness, chills, tiredness, headache

Status in the Philippines: Emergency use authorization (EUA) granted

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Moderna vaccine (mRNA-1273)

Efficacy: 94 percent based on phase 3 clinical trials

Age range: 18 years and older, but frail persons 95 years and above were not included in trials

Regimen: 2 doses at an interval of 28 days.

Logistics: Prior to administration, this vaccine is stored in vials good for 10 doses each at -25 to -15 degrees Celsius. After thawing, unopened vials may be stored at 2 to 8 degrees Celsius for up to 30 days. Once opened, a vial should be discarded after six hours.

Common side effects: pain, swelling, redness, chills, tiredness, headache

WHO said both the Pfizer-BioNTech and Moderna vaccines should not be given to individuals with a history of anaphylaxis to polyethylene glycol (PEG).

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Adenovirus vectors

Vaccines using adenovirus vectors, or engineered viruses, were developed by AstraZeneca with University of Oxford, Gamaleya National Center of Epidemiology and Microbiology of Russia, and Johnson & Johnson subsidiary Janssen Pharmaceuticals.

Gamaleya said vectors are viruses without the gene responsible for replication. These no longer pose any threat of infection, but are used to transport genetic material from a different virus - in this case the Sars-CoV-2 - into a human cell.

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AstraZeneca vaccine (AZD1222)

This was developed using chimpanzee adenovirus vector ChAdOx1, which was modified to contain the genetic material for making the Sars-CoV-2 spike protein.

Efficacy: 90 percent when given as a half dose followed by a full dose at least one month apart; 62 percent when given as two full doses at least one month apart; 70 percent average efficacy

Age range: 18 years and older

Regimen: 2 doses

Logistics: Storage at 2 to 8 degrees Celsius for at least six months and administered within existing healthcare settings

Common side effects: pain, headache, fatigue, myalgia, malaise, fever, chills and nausea

Status in the Philippines: EUA granted

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Sputnik V (Gam-Covid-Vac)

This vaccine was developed by Gamaleya based on heterologous recombinant adenovirus. The V in Sputnik V stands for vaccine, not the Roman numeral for five.

Efficacy: 91.6 percent based on phase 3 clinical trials: 100 percent against severe Covid-19

Age range: 18 years and older, including those over 60 years old, as approved by Russia

Regimen: 2 doses with 21-day interval

Logistics: Storage at 2 to 8 degrees Celsius

Common side effects: pain, hyperthermia, headache, asthenia, and muscle and joint pain

Status in the Philippines: EUA application pending

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Janssen vaccine

Johnson & Johnson, parent firm of Janssen Pharmaceuticals, announced phase 3 clinical trials results on January 29. The vaccine was tested against moderate to severe Covid-19.

Efficacy: 72 percent in the United States, 66 percent in Latin America and 57 percent in South Africa, 28 days after a single dose. Overall, it was 85 percent effective in preventing severe disease.

Age range: 18 years and older

Regimen: 1 dose

Logistics: Storage at 2 to 8 degrees Celsius

Common side effects: pain, fever

“Janssen is less efficacious in preventing symptomatic disease overall but it’s very efficacious in preventing severe disease,” Rasmussen observed.

She also noted that the clinical trial results showed that the vaccine can also partly protect against the B.1.351 variant, which was present in nearly all cases studied in South Africa.

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Inactivated virus

An inactivated vaccine contains severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) that has been killed so that it can’t make a person sick.

An example is the CoronaVac developed by Sinovac Life Sciences Co. of China.

CoronaVac (Sinovac)

Efficacy: 50.38 percent based on phase 3 clinical trials by Butantan Institute in Brazil; 91.5 percent based on phase 3 clinical trials in Turkey: 65.3 percent in Indonesia

Age range: 18 years and older

Regimen: 2 doses at interval of 28 days

Logistics: Storage at 2 to 8 degrees Celsius

Common side effects: pain, headache and fatigue

Status in the Philippines: EUA application pending

Other inactivated vaccines that are being considered are those developed by Sinopharm and Bharat Biotech.

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Subunit

A subunit vaccine, like the inactivated vaccine, does not contain live components of the pathogen and is, thus, very safe, according to the WHO. It contains only the antigenic parts of the pathogen.

Novavax Inc. said its vaccine NVX-CoV2373 contains an engineered spike protein which was made using its recombinant nanoparticle technology and encoded with the genetic sequence of Sars-CoV-2.

The company then combined this with its proprietary adjuvant, a substance added to a vaccine to generate a stronger immune response.

“A primary benefit of our adjuvanted platform is that it uses a very small amount of antigen, enabling the rapid creation and large-scale production of combination vaccine candidates that could potentially address multiple circulating strains of Covid-19,” said Gregory M. Glenn, president of Research and Development at Novavax.

NVX-CoV2373

Efficacy: 89.3 percent in United Kingdom phase 3 clinical trials, where more than 50 percent of participants were infected with the B.1.1.7 variant; 60 percent in phase 2b clinical trials in South Africa, where most volunteers carried the B.1.351 variant

Age range: 18 to 84 years old in phase 3 clinical trials

Logistics: Shipped in a ready-to-use liquid formulation that requires storage at 2 to 8 degrees Celsius

“This is the first Covid-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa,” said Professor Shabir Maddi, executive director of the Vaccines and Infectious Diseases Analytics Research Unit (Vida) at Wits, and principal investigator in the Novavax Covid-19 vaccine trial in South Africa.

Novavax president and CEO Stanley Erck added that the vaccine also showed significant clinical efficacy against the UK variant.

Other subunit vaccines are those from Clover and Anhui Zhifei.

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Vaccine czar Carlito Galvez Jr. said the first shipments under the Covax initiative are expected in mid-February.

These are the 117,000 doses of Pfizer-BioNTech and an initial shipment from AstraZeneca, which will deliver 5,500,800 to 9,290,400 doses in the first two quarters or 2021.

The Philippines will get over 9.4 million doses of the Pfizer-BioNTech and AstraZeneca vaccines under Covax, Galvez announced on January 31.

Read: Covax allots 9.4M doses of Pfizer, AstraZeneca vaccines for PH

Galvez also earlier said Sinovac will deliver an initial shipment of 50,000 doses on February 20, an additional 950,000 doses in March, and two to three million doses a month until December 2021. A total of 25 million doses have been committed by Sinovac.

By the third quarter of 2021, AstraZeneca is expected to start deliveries of another 17 million doses for the private sector and local government units (LGUs).

Galvez also said he has secured 30 million doses from Novavax through vaccine manufacturer Serum Institute of India and was set to finalize a deal for 20 million doses from Moderna.

As of January 31, negotiations were ongoing with the Russian Direct Investment Fund for Gamaleya’s Sputnik V and with Janssen Pharmaceutical for its single-dose vaccine.

Procurement

Procurement of vaccines is done in three phases.

The first phase involves preliminary meetings and the signing of a non-disclosure agreement, which prevents both parties from releasing confidential information such as the price of the vaccine.

The second phase begins with the exchange of the term sheet, which contains the number of doses, purchase price, target date of signing of the binding supply agreement, payment and effectivity dates, delivery schedules, and other obligations of each party.

Under the third phase, the national government submits the term sheet to the financing banks for clearance, and the parties sign the supply agreement in the form of advance market commitment, supply agreement or research and development investment.

Before delivery and payment of balance, a vaccine must be covered by EUA to allow its use in the Philippines.

Procurement of vaccines by LGUs must be coordinated with the national government, through a tripartite agreement with the NTF and the DOH.

This is because an EUA allowing the use of a vaccine that is still under clinical trials does not cover the commercial use of the vaccines.

This means that manufacturers cannot sell directly to the LGUs nor to any entity, unless they are under the vaccine initiative of the national government, the Food and Drug Administration said on January 11.

Responding to a clamor for LGUs to be allowed to directly negotiate with the drug companies, the DOH assured that “delivery of services are biased towards the vulnerable and the disadvantaged.”

Options

Immunologist and allergist Purvi Parikh of NYU Langone, during the January 29 webinar for journalists, said having the vaccines in multiple platforms provides options to the public.

Besides, she said it would allow scientists to test which platform would work against Sars-CoV-2 variants as they emerge.

So far, she said the mRNA platform appears to be relatively easier to update and tweak.

“Unfortunately, there are not enough mRNA vaccine doses, so we need these other vaccines,” she added.

Parikh also noted that these candidate vaccines against Covid-19 have shown better efficacy than the flu vaccine.

“If you think about it, the influenza vaccine that is distributed every year has only 40 to 50 percent efficacy depending on the year,” she said.

She also assured that any side effects are temporary, lasting 24 to 48 hours only, and are neither severe nor persistent.

The prices of these vaccines vary and “pricing deals are often kept secret by the drug companies even though many of them benefit from public funds and public funded research,” Unesco director for freedom of expression Guy Berger lamented in the same webinar. (SunStar Philippines)

Next Part 3: Government prepares for vaccine rollout

Back to Part 1: A shot in the arm