Sputnik-V Covid-19 (SARS-CoV-2) Vaccine: Effective and Safe?

Sputnik-V Covid-19 (SARS-CoV-2) Vaccine: Effective and Safe?

This was the first vaccine against Covid-19 (SARS-CoV-2) to be used for public vaccination. Sputnik-V/Gam-COVID-Vac was launched in Russia in September 2020, three months before any other vaccine. Several million people have received this vaccine by now; it is approved for use in 68 countries.

The Gamaleya National Research Centre for Epidemiology and Microbiology (Russia) developed this vaccine to protect against Covid-19 (SARS-CoV-2). Also known as Gam-COVID-Vac, this vaccine is unique in using two different recombinant adenoviral vectors for its two doses. The vaccine requires two doses, 21 days apart.

Both the adenoviruses are similar. They enter human cells and stimulate them to produce the Covid-19 virus spike protein. The adenovirus itself is modified so that it cannot multiply in the human body.

The cells infected by the vaccine are destroyed by immune system cells, exposing the spike protein. The immune system thus gets introduced to the Covid-19 viral component.

Early Data

The Institute published phase 1 and 2 trial data as far back as September 2020. The vaccine generated good levels of spike protein antibodies, including neutralizing antibodies. Neutralizing antibodies prevent the virus from binding to receptors, entering the cells, and causing disease.

The vaccine also produced T-cell responses, which is likely to provide long-term protection. The vaccine was seen to be safe.

The Sputnik-V vaccine was under a cloud because it was pushed into public use without a phase 3 trial. Recently, more data has been published in the Lancet, removing the doubts.

Vaccine Technologies

Vector vaccines: Oxford/AstraZeneca, Sputnik-V, the Johnson and Johnson vaccine, a vaccine from CanSino Biological Inc/Beijing Institute of Biotechnology, and a vaccine from Janssen Pharmaceutical Companies.

Whole-cell inactivated vaccines: Covaxin, SinoVac, and Sinopharm.

mRNA-based vaccines: BioNTech/Pfizer vaccine, Moderna/National Institute of Allergy and Infectious Diseases vaccine.

Adjuvanted recombinant protein nanoparticles: Novavax NVX-CoV2373.

Using adenoviruses as vehicles for vaccination is a recent technology, but not unique. The Gamaleya Institute has experience with it, having used it to make a vaccine for the Ebola virus.

What is an Adenovirus Vector?

Like the Oxford/AstraZeneca and the Johnson and Johnson vaccines, Sputnik-V uses a modified adenovirus vector.

Adenoviruses are viruses that infect humans and animals. Scientists genetically engineer the virus to carry the DNA that codes for the Covid-19 virus’s spike protein. Antibodies against this protein will prevent the Covid-19 virus from attaching to and entering human cells.

The adenovirus is modified so that it cannot multiply. However, the spike protein DNA generates the required immune response.

Recent Data on Efficacy

The ongoing phase 3 trial intends to enroll 40,000 participants. The investigators have published interim findings, including data on almost 20,000 participants.

All the participants were over the age of 18 years. About a quarter of them had comorbidities. They were randomly chosen to receive vaccine or placebo; about 75% received the vaccine.

Participants received two doses at an interval of 21 days.

Confirmed Covid-19 infection was seen in 1.3% of the placebo group, and 0.1% of the vaccine recipients. Vaccine efficacy after 21 days of the first dose was 91.6%.

Among those that developed Covid-19 after vaccination, disease severity decreased with time since vaccination.

What About Severe Covid-19?

Among the 14,964 people who received SputniK-V, there was no case of moderate or severe Covid-19 disease after 21 days of the first dose, compared to 20 among the 4,902 people who were given the placebo.

The vaccine has 100% efficacy against severe disease and death. However, between day 15 and 21, this protection was 73.6%, increasing to 100% only after Day 21 after the first dose.

Several participants developed Covid-19 in the first few days after the vaccination. Most of them had probably been infected before the vaccine was administered. Since protective immunity had not developed, the disease followed its natural course.

Of the vaccine recipients who developed Covid-19 in the week after vaccination, two died. One had cardiovascular comorbidity; the other an endocrine disease.

Laboratory Studies

Vaccines can protect by generating antibodies (humoral immunity) and by stimulating cellular immunity. The investigators measured both forms of immune response to Sputnik-V.

To be technical, 98% of persons that received the vaccine developed antibodies specific to the receptor-binding domain of Covid-19 glycoprotein S, compared to 15% of people in the placebo group.

Cellular immunity was measured by the production of interferon-gamma (IFN-γ) by mononuclear cells stimulated with Covid-19 glycoprotein S in the laboratory. A sample of the vaccine recipients was tested; all showed significantly higher levels of IFN-γ production.

How Long Does Protection Last?

That is not known yet. The investigators are monitoring the vaccine recipients and intend to enroll more participants.

We will know the duration of protection as time passes.

Currently, we do not know whether two doses are adequate, or if further doses will be required.

What About Variants?

The Covid-19 virus changes its structure, giving rise to variants. There is much concern that this may make antibodies and other immunity ineffective. This immune escape is worrisome.

The various vaccines in use around the world have different protective efficacies against these variants. The Sputnik-V vaccine is effective against the B.1.1.7 variant (which was first identified in the UK). Unfortunately, it appears less effective against the B.1.351 variant (first identified in South Africa).

Is Sputnik-V for Everyone?

Though people were comorbidities were included, the study design excluded:

  • Children under 18 years.
  • Pregnant and breastfeeding women.
  • People on steroid and immunosuppressive treatment.
  • People with HIV, hepatitis B or C, tuberculosis, and other chronic diseases.
  • Cancer.
  • Drug or alcohol addiction.

This doesn’t mean Sputnik-V cannot be given to these people. The vaccine has not been tested; we do not know if it is safe and effective in these people. Future studies should provide evidence about the safety and efficacy of the vaccine in these people.

Safety of Sputnik-V

Several of the vaccine recipients had minor adverse effects.

  • Injection site pain
  • Flu-like illness
  • Headache
  • Weakness and tiredness
  • Muscle and joint pain.

There were no severe adverse events or deaths attributable to the vaccine. Sputnik-V does not appear to have dangerous adverse effects.

The investigators mention that there were no cases of cranial sinus thrombosis, as have been seen with other adenoviral vector vaccines.

Advantages of Sputnik-V

A vaccine with adenoviral vectors has the advantage of stimulating both antibodies and cell-mediated immunity. The two-dose schedule will generate long-lasting immunity.

A concern with such vaccines and schedules has been that the recipients would develop an immune response to the viral vector. This would prevent the second dose of the vaccine from acting. Sputnik-V uses two different viral vectors to circumvent this issue.

Considering the global shortage of vaccines for Covid-19, the high efficacy after one dose is a ray of hope.

Gamaleya is willing to share its technology so that countries can produce their own requirements. A significant advantage is that it is inexpensive to produce.

Technical Stuff

The Sputnik-V vaccine utilizes a heterologous prime-boost regimen. What does this mean?

Vaccines in use till now use homologous prime-boost regimens. We administer two or more doses of the same vaccine to generate immunity and protection.

A heterologous prime-boost regimen uses two different vaccines, and should stimulate better antibody and cellular immunity.

The Sputnik-V vaccine uses two different recombinant adenoviruses. The first dose is the rAd26, and the second is the rAd5. Both these vectors carry the gene for the full-length Covid-19 glycoprotein S.

Availability

Over 60 countries have approved this vaccine for use; it is an option for about 40% of the world’s population.

It is available in two forms.

  • Liquid vaccine, which needs storage at -18° C.
  • Freeze-dried vaccine, which can be stored at 2-8° C.

Both forms of the vaccine are given intramuscularly, and are effective in generating antibodies and cellular response.

Sputnik Light

This is a single-dose vaccine.

It uses only one component of the Sputnik-V vaccine, the recombinant human adenovirus rAd26.

The efficacy of Sputnik Light is 79.4%, studied 28 days after the injection was administered.

WHO Recommendations

The World Health Organization recommends that any vaccine meant for use in an outbreak should:

  • Have an efficacy of at least 50%
  • Be suitable for older people
  • Not need more than two doses
  • Protect for at least six months.

Sputnik-V meets all the conditions but the last, as the study has not yet reached the six-month follow-up.

Conclusion

Dozens of vaccines were in development half a year ago, but many had to be abandoned. Sputnik-V/Gam-COVID-Vac is one of the few vaccines that have been proved to be effective and safe.

As more and more of our population gets vaccinated, life may turn towards normalcy. Vaccinated people can do many things safely, but Covid-19 appropriate behaviour will still be required to control this dreadful pandemic.

References

Logunov DY et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia.

Logunov DV et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia.

Preprint: Ikegame S et al. Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants.

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