Here is a comparison of the 5 major vaccines, now that results for the Novavax and Johnson&Johnson/Janssen (J&J) vaccines have been announced this week.
Efficacy by country where trials were conducted -
| Vaccine |
Doses |
Overall
|
Against
Severe disease
|
U.S.
|
U.K.
|
S. Africa
|
L. America |
| Moderna |
2 |
94.1% |
100% |
95% |
- |
- |
- |
| Pfizer/BioNTech |
2 |
95% |
90%
|
95% |
- |
- |
- |
| AstraZeneca |
2 |
62% |
100% |
- |
60% |
- |
64.2% |
| AstraZeneca
(½ + full dose)
|
2 |
90% |
100% |
- |
90% |
- |
- |
| J&J |
1 |
66% |
100% |
72% |
- |
57% |
66% |
| Novavax |
2 |
- |
100% |
- |
89.3% |
49.4% |
- |
Notes:
- The efficacy numbers differ but all vaccines prevent severe illness and death.
- The J&J and Novavax trial periods were later than the other three, a period with greater infection rates and possible variants.
- J&J notes
- J&J efficacy numbers are for preventing moderate to severe disease, but not mild cases.
- J&J vaccine reduced severe disease alone by 85% after 28 days
- J&J vaccine reduced hospitalizations and deaths to zero after 28 days, even in S. Africa (this seems to contradict the previous statement) www.jnj.com/...
- Efficacy against severe disease increased over time with zero cases in the vaccinated group reported after day 49.
- Unlike other companies, J&J has not yet published confidence interval values or actual counts of patients with disease in the vaccine or placebo group. This is raising some eyebrows and generating some skepticism for the J&J numbers.
- The number of cases with severe disease in the placebo group was very small in general. The definition of severe cases varies across vaccine trials. Pfizer had 1 case of severe illness in the vaccine group. Novavax had 1 severe case in the placebo group in U.K. and S. Africa. J&J had approximately 40-60 hospitalizations and deaths in the whole trial, all in the placebo group (source).
Efficacy values for specific strains
We now have vaccine data against the major emerging virus variants, thanks to the late clinical trials by Novavax and J&J.
| Vaccine |
Overall
|
Original Strain
D614G
|
UK
Strain B.1.1.7
|
S. Africa
Strain B.1.351
|
| Moderna |
95% |
95% |
- |
- |
| Pfizer/BioNTech |
95% |
95% |
- |
- |
| AstraZeneca |
62% |
62%
U.K. and L. America
|
- |
- |
|
AstraZeneca
(½ + full dose)
|
90%
|
90%
U.K. and L. America
|
- |
- |
| J&J |
66% |
72%
U.S. and L. America
|
- |
57% |
| Novavax |
- |
96%
(in U.K)
|
85.6% |
49.4%
60% for HIV-neg patients
|
Notes:
- D614G is the dominant variant today and it replaced the original strain from Wuhan.
- B.1.1.7 is prevalent in the U.K., is known to be 50% more transmissible and 29% more lethal.
- The slightly lower efficacy value for Novavax against B.1.1.7 in U.K hints that B.1.1.7 may be somewhat resistant to current vaccines
- The B.1.351 variant is cause for concern as there is evidence that B.1.351 can re-infect patients who have recovered from earlier strains and it is somewhat resistant to antibodies in lab tests.
- There is another strain called P.1 from Brazil, which has very similar mutations as B.1.351.
- All these variants have been found in the U.S.
- The Novavax results from South Africa (mainly for the B.1.351 variant) are very limited, based on a Phase 2b clinical trial, with only 4,400 patients. The efficacy numbers from S. Africa should be used with caution when comparing vaccines. The 95% confidence interval range is very large.
- Moderna announced some results recently, based on in vitro lab testing, that the vaccine is effective against the B.1.1.7 and B.1.351 variants, a little less so against the B.1.351 variant. See www.dailykos.com/… for details. Pfizer/BioNTech announced similar results for the B.1.1.7 variant.
All of these vaccines are less effective, but not ineffective, against variants. After all, the new variants have a lot of genes in common with the old ones. But the B.1.351 variant is cause for concern and all vaccine producers are creating vaccine variants against it.
Clinical Trial Size
| Vaccine |
Total |
US
|
UK
|
S. Africa
|
L. America |
| Moderna |
30,000 |
30,000 |
- |
- |
- |
| Pfizer/BioNTech |
44,000 |
44,000 |
- |
- |
- |
| AstraZeneca |
11,636 |
- |
7,548 |
- |
4,088 |
| J&J |
43,783 |
19,302 |
- |
6,576 |
17,905 |
| Novavax |
19,400 |
- |
15,000 |
4,400 |
- |
Note that the number of participants in S. Africa is relatively small.
Other Info
| Vaccine |
Moderna |
Pfizer/BioNTech |
AstraZeneca |
J&J |
Novavax
|
| Type |
mRNA |
mRNA |
DNA/ Adenovirus |
DNA/ Adenovirus
|
Protein |
| Dose |
2 |
2 |
2 |
1
|
2 |
| Days between doses |
28 |
21 |
28 |
-
|
21 |
| Storage Temperature |
-20oC
-4oF
|
-70oC
-94oF
|
2°C to 8°C
36oF to 46oF
|
2°C to 8°C
36oF to 46oF
|
2°C to 8°C
36oF to 46oF
|
| Date of Phase 3 Prelim. Results |
Nov 16, 2020 |
Nov 18, 2020 |
Nov 23, 2020 |
Jan 29, 2021 |
Jan 28, 2021 |
| Report Published |
Yes |
Yes |
Yes |
No |
No |
| Approx. cost per dose |
$25 - $37 |
$19 - $23 |
$4 |
$10 |
$16 |
| FDA Emergency Approval |
Yes |
Yes |
No
Approved in other countries
|
Next week or two? |
? |
| Expected doses for the U.S. |
100m by end of March, 200m by end of June |
170m by the end of June |
|
100m by end of June |
150m a month, starting May or June, globally |
Notes:
- The non-mRNA vaccines have the distinct advantage of not requiring ultra-cold temperatures during transportation and storage.
- The cost per treatment is 2x for all vaccines except J&J.
- Novavax should get approval in the U.K. soon (I think), not sure about the U.S., since the clinical trial in the U.S. won’t produce results until March. They plan to apply anyways based on the U.K. results. finance.yahoo.com/...
Vaccine Types
- mRNA: The Moderna and Pfizer/BioNTech vaccines contain Coronavirus spike protein mRNA strands encased in lipids, which enter the human cell. The human cell then produces Coronavirus spike proteins.
- Viral-Vector: The J&J/Janssen and AstraZena/Oxford vaccines use an Adenovirus to carry the Coronavirus spike protein DNA into the human cell. The human cell then produces Coronavirus spike proteins.
- Protein-based: The Novavax vaccine contains (ready-made) Coronavirus spike protein nanoparticles, grown in the lab, in insect cells. The vaccine also contains a saponin-based adjuvant (extracted from the soapbark tree native to Chile), which boosts the immune response to produce more antibodies.
Vaccines also “train” the immune system to generate additional antibodies in the future if a person gets infected by the virus.
See www.nytimes.com/... for more details about how these vaccines work.
Keep in mind that, in two-dose vaccines, it is the 2nd dose that generates the stronger immune reaction. And it takes several weeks to build up after that. Among some of the elderly, the first dose generates very little immune response. See https://twitter.com/GuptaR_lab/status/1355283902202523653
The Virus Variants (aka strains)
Viruses mutate regularly, but most mutations do not affect its infectiousness or lethality. But a few mutations have emerged that make the virus more efficient in infecting human cells and in evading antibodies from previous infections and from monoclonal antibody therapies. The 3 variants shown below, which each contain multiple mutations, are the ones of most concern at this time and are likely to become the dominant ones in the world soon.
|
B.1.1.7 |
B.1.351 |
P.1 |
| Other names |
501Y.V1 |
501Y.V2 |
501Y.V3
|
| First Identified in |
U.K. |
S. Africa |
Brazil |
| Date of Identification |
Sep 2020 |
Oct 2020 |
Dec 2020 |
| Mutations |
23 |
21 |
17 |
| Spike Mutations |
8 |
9 |
10 |
| Key mutations |
N501Y, E69/70 deletion, P681H, Y144 deletion, orf1ab deletion
|
N501Y, E484K, K417N, L18F, D80A, orf1ab deletion |
N501Y, E484K, K417T, L18F, H655Y, orf1ab deletion |
| Increased transmissibility |
>40% |
Probably similar to B.1.1.7 |
suspected |
| Increased lethality |
>29% suspected |
Probably similar to B.1.1.7 |
? |
| Reduced vaccine efficacy |
likely |
Yes |
likely |
| Re-infection (immune escape) |
? |
Some evidence from S. Africa |
suspected |
The N501Y mutation affects the receptor binding domain (RBD) of the spike protein, which the virus uses to clasp onto the ACE2 receptors on the surface of human cells. The mutation potentially allows the virus to bind more tightly to ACE2 receptors, facilitating entry into the cell.
There is some evidence that the E484K mutation makes the virus more resistant to antibodies.
The reduced vaccine efficacy for B.1.351 is supported by results from Novavax and J&J and also by in vitro tests conducted in Africa.
B.1.351 and P.1 emerged independently in areas with high levels of previous infections.
I don’t think the P.1 variant played much of a role in the clinical trials held in Brazil.
We will write a separate diary on Coronavirus variants and their implications on vaccines and public health policy.
Vaccine Variants
The technology used in these vaccines makes it quite easy to modify them for new variants. Once the genetic sequence of the new variant is known, the mRNA/DNA/protein can easily be modified accordingly.
- Novavax has plans to begin clinical development on a vaccine targeted to the variants.
- Moderna and BioNTech are also creating modified vaccines to address B.1.351.
- Others will likely follow suit.
The new vaccines might be delivered as a 3rd dose or a mix of vaccine variants in the first or second dose.
It is not clear what level of clinical trials will be needed for these variant vaccines and how long it will take. Expectations are for approval in fall.
The Johnson & Johnson Vaccine
There seem to be a lot of differing opinions on the J&J vaccine. Some are concerned about the 66% efficacy number and the lack of trial data so far. But others point out that the efficacy numbers, as stated, are acceptable and point out that —
- Efficacy was 72% in the U.S. and L. America
- J&J vaccine reduced severe disease by 85% after 28 days
- J&J vaccine reduced hospitalizations and deaths to zero after 28 days, even in S. Africa
- Efficacy against severe disease increased over time with zero cases in the vaccinated group reported after day 49
- Single dose
- Lower cost
- No ultra-cold refrigeration requirement
-
J&J has stated that they can produce 1 billion doses per year starting in 2021
Here is another summary of the J&J vaccine.
Johnson & Johnson is running another large study, to test a two dose regime, given 57 days apart. The phase 3 trial started on Nov 15, 2020. Recruitment for 30,000 participants should be done by March 2021. Results of the two-dose study are expected in summer or fall.
There is also some negative coverage of the Novavax vaccine in that it is less effective (49.4%) against the B.1.351 from S. Africa. But keep in mind, that the number is 60% for HIV-negative patients and we do not have efficacy numbers for the mRNA vaccines against B.1.351. We cannot assume that the mRNA vaccines will do any better against B.1.351. The Novavax vaccine has a few other advantages -
- It is marginally better than the mRNA vaccines on the original virus strain
- It has proven results against both B.1.1.7 and B.1.352 strains
- No ultra-cold refrigeration requirement
- Lower vaccine amount is needed because of the effect of the adjuvant
- Novavax has stated that they can produce 2 billion doses per year
Vaccines reserved and administered around the world
www.bloomberg.com/… has this interesting tracker of vaccine doses reserved around the world by country and by manufacturer. Over 8.49 billion reserved!
From www.bloomberg.com/…, here are the stats on doses administered so far. We have a long way to go, but the pace is picking up.
|
WORLD |
USA |
| Doses administered |
98.3 million
across 62 countries
|
31.8 million |
| Recent doses per day |
4.2 million |
1.35 million |
| Population |
7,674 million |
328 million |
Discussion
Overall, the Novavax and J&J results bode well for the future, since we need billions of doses to get the world population vaccinated soon. The longer the virus lingers and thrives in the population, the higher the chances of it mutating, becoming more infectious and becoming resistant to existing vaccines. And others have pointed out, it does no good if one country is fully vaccinated but others aren’t; the virus will thrive and mutate in countries with low levels of vaccination and it will then land on other shores.
Speed of vaccination is of the essence right now, so that the virus spread can be brought under control soon.
Speed of vaccination is also driving the debate whether we should use up all vaccine stock right away and administer the first dose to the maximum number of individuals, and perhaps delay the 2nd dose by a few weeks, rather than reserve and store away the second doses and administer them on time. The other side of the coin is that the delayed 2nd dose might give the virus a chance to evolve against the vaccine inside patients where certain variants selectively survive against a diminished immune response.
There is genuine concern that the B.1.1.7 and B.1.351 variants, and possibly the variant from Brazil P.1, will become dominant worldwide in the next few months.
There is also concern that as vaccination levels rise, it will put selection pressure on the virus to evolve into B.1.351 or P.1 -like variants, that can evade antibodies generated by current vaccines. It might mean periodic updates to vaccines and annual shots, just like the flu.
And let’s not even talk about what would have happened with virus mutations if trump had won the election and gone ahead with the let-everyone-get-infected herd-immunity racket.
Epilogue
Which vaccine should you get? I do not have an opinion since I am not a medical professional. Most experts agree that we should get whichever one is available. The difference in efficacy values is not significant. More importantly, all of these vaccines prevent severe illness and death.
Speed of vaccination is of the essence right now, so that the virus spread can be brought under control soon. More virus means more chances of dangerous mutations.
All this also means that we should not let our guard down after getting the vaccine. Social distancing and masking will remain useful tools even after vaccination, until most of the population is vaccinated and infection rates reduce to a trickle.
OK, let’s discuss vaccines.
Further Reading
- How the Novavax Vaccine Works — www.nytimes.com/…
- Novavax press release — ir.novavax.com/…
- Novavax Healthcare Conference slides — www.novavax.com/…
- Novavax trial results summary slides — www.novavax.com/…
- Johnson & Johnson Announces Single-Shot Janssen COVID-19 Vaccine Candidate Met Primary Endpoints in Interim Analysis of its Phase 3 ENSEMBLE Trial — www.jnj.com/…
- AZD1222 Oxford Phase III trials interim analysis results published in The Lancet — www.astrazeneca.com/…
- A Guide to Emerging SARS-CoV-2 Variant — www.the-scientist.com/...
- Emerging SARS-CoV-2 Variants — www.cdc.gov/…
- SARS-CoV-2 lineages — cov-lineages.org/…
- covariants.org
- SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma — www.biorxiv.org/…
- mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants — www.biorxiv.org/...
- A comparison of the Pfizer/BioNTech and Moderna COVID-19 vaccines — www.dailykos.com/…
- Moderna says COVID-19 Vaccine is effective against variants from U.K. and S. Africa — www.dailykos.com/…
