COVID-19 Vaccines: What We Know So Far!

- By Dr. Vipin M. Vashishtha, MD @vipintukur

The Global Scenario:

Ten different Covid-19 vaccines have shared their Phase III data.

2 based on mRNA,
4 on viral vector,
3 on inactivated
1 on protein subunit platform.

1/n

After 4 months of their trials, now there is a definite gradient in their performance:

Highly efficacious: mRNA,
Moderate: Viral vector,
Low to Moderate: inactivated vaccines.

(based on Trial Data and Post-trial Population Data)

2/n

Efficacy (Point estimates as per published/shared data):

Pfizer 95%
Moderna 94.1%
Sputnik-V 91.6%
Novavax 89.3%
AstraZeneca (AZ) 62-90%
Sinopharm’s (BBIBP-CorV) 79%
Covaxin 78%
JNJ 72%
CanSino’s 65.7%
Sinovac’s (CoronaVac) 50.4%

3/n

Quality of evidence (Confidence):

> Highest (Real-world use, Effectiveness data & Publication of Efficacy trial):

Pfizer
AstraZeneca
Moderna

> Moderate (Real-world use, Publication of efficacy trial):

JNJ
Sputnik-V
Sinopharm
Novavax

(contd)

4/n

>Low-moderate (Real world data, no publication of efficacy trial):

CanSino
Sinovac
Covaxin

5/n

Israel, Chile, Bahrain, US & UK are the 5 leading countries as far as the highest share of the fully vaccinated population is concerned.

Sinovac’s CoronaVac vaccine fared poorly in Seychelles & Chile.

6/n

Pfizer & AZ vaccines have shown real-world effectiveness & population level impact. Though some level of confounding effects of non-pharmaceutical interventions was also present.

Most vaccines have the highest efficacy against severe disease & deaths.

7/n

No vaccine is 100% efficacious against SARS-CoV-2 SARS-COV-2 transmission infection (NO STERILIZING IMMUNITY).

Except for Pfizer/Moderna vaccines, most vaccines have only modest efficacy against transmission.

8/n

Breakthrough infections observed with almost all vaccines. Most mild & moderate, deaths are also seen in fully vaccinated (out of 5800 breakthrough cases with mRNA vaccines in the US, 7% hospitalized & 74 died)

9/n

Most vaccines have comparatively lower efficacy in the elderly & comorbidities than in younger and healthy people.

Most gene-based vaccines (mRNA & Viral vector) have high reactogenicity profile.

10/n

Adenovirus vector-based vaccines (AZ & JNJ) have rare, serious adverse events called VITT (vaccine-induced immune thrombotic thrombocytopenia).

Incidence varies from 1 case in 40 000 to 1 in 100 000, but the BENEFITS FAR OUTWEIGH THE RISKS.

https://www.nejm.org/doi/full/10.1056/NEJMe2106315

11/n

Efficacy against variants:

>Most vaccines have only very modest reductions in efficacy against UK’s B117 & Brazil’s P1 variants.

>Most vaccines have lower efficacy against South Africa’s B1351 variant (containing E484K mutation).

12/n

> AZ vaccine has got only 10% efficacy against B 1.351.

>JNJ (57%) & Novavax (49%) had major reductions in efficacy trials.

>Sputnik-V, Pfizer & Moderna vaccines have reduced neutralization against B1.351.

13/n

> Pfizer vaccine has shown intact efficacy against B1.351 in Qatar in real-world evidence after 2 doses.

>Nevertheless, most leading vaccines are developing boosters with revised formulation to tackle the B1.351 variant.

14/n

So far, natural infection-induced protection seems to be more lasting than vaccine-induced, particularly in the context of non-mRNA vaccines.

>Things are still evolving. This is an observation based on 6-7 months post the trial reports. Too early to conclude anything.

15/n

> Also, the response of the human immune system to the invading virus is not uniform. Many patients with a severe infection also fail to have a good amount of Memory B cells.

>Whereas, with vaccines - such uncertainty can be avoided.

16/n

Only 4 vaccine candidates elicited several folds higher titers of neutralizing antibodies (NAbs) than natural infection (NAbs titers measured in human convalescent serum):

Pfizer
Moderna
Novavax
Sputnik-V.

However, natural immunity is much broader.

17/n

We know that natural infection provides at least 8 months of protection.

>mRNA vaccines are found to provide protection at least for 6 months without any appreciable loss of efficacy.

>Vaccines like inactivated & AZ vaccine may provide a lesser duration of protection.

18/n

Natural infection may provide resistance against immune evader variants also since there are immune responses against not only against S protein but against other antigens of the virus.

Further, the variants do not have changes in T-cell epitopes.

19/n

Most vaccines elicit both humoral and T cell immunity.

> However, viral vector vaccine, particularly the AZ vaccine has got particularly good CD8 cell response which kills the virus-infected cell and ameliorates the severity of the disease.

20/n

Those had natural infection can ideally wait for THREE MONTHS for their Covid vaccine shot. (minimum time to wait is at least 4-6 weeks)

In previously infected individuals with anti-spike IgG positive individuals, only ONE DOSE of mRNA vaccine is sufficient.

21/n

Though no official recommendation from the WHO, still pregnant women can have the vaccine at any stage of pregnancy. Strong data for 3rd trimester with mRNA vaccines.

> FIGO and FOGSI have recommended vaccination of Pregnant women (2nd, 3rd trimester).

22/n

> No known risk in giving COVID-19 vaccines to women who are breastfeeding.

>Women who are breastfeeding should be encouraged to continue breastfeeding after being vaccinated.

23/n

No need to avoid becoming pregnant after having the vaccine.

There is no evidence to suggest that COVID-19 vaccines will affect fertility.

24/n

Several vaccines are now conducting trials in the Pediatric population.

Pfizer - 100% efficacy in 12-15 yrs old.
Moderna - Trials in 6mo to 12 yrs (inUS) & 5-11 yrs (in Canada).
JNJ 12-17 yrs.
Sinovac 3-11 yrs.
Novavax 12-17 yrs.
AZ has paused their trial in 6-17 yrs.

25/n

Thank you, Dr. Vipin Sir @vipintukur for this.

To those with more queries, join us on Twitter Spaces on Tuesday, 11 May, 8:30pm with @vipintukur Sir and @ProfSomashekhar Sir.