Lower efficacy in a vaccine does not translate into it being sub-standard

In conversation with many Guyanese folks, following my letter published in this newspaper on Jan. 20, I was asked my opinion on taking a vaccine with a lower efficacy than that reported for two doses of the Pfizer/BioNTech, Moderna and Oxford/AstraZeneca (known as Covishield in India and manufactured by the Serum Institute for COVAX) vaccines. It seems many believe that lower efficacy and the rapid pace at which vaccines have been developed translates to a substandard product. This is misleading, hence this letter. I would like to make the following points:

1. Efficacy, safety and the regulatory process

High efficacy vaccines are at the forefront of mainstream news and have been approved by regulatory bodies in lead nations in the developed world. However, due to the current vaccine equity problem that the world faces these may not be available in adequate quantities to the developing world for timely vaccination. Waiting on a vaccine that you deem superior, for vaccination, in my view is irresponsible as you’re

not only leaving yourself susceptible to infection but slowing down the goal of vaccination campaigns – to get as many immunized to the point where person to person transmission is highly unlikely.

So, how would I decide on a vaccine? First a bit on vaccine development and approval process. Vaccine development starts in the lab in an exploratory stage after which candidate vaccines undergo pre-clinical testing for an immune response and evidence of protection using cells, tissue samples or animals. Once a good candidate is found, researchers submit results to regulatory bodies for review. If approved the vaccine candidate undergoes human clinical trials in three phases to determine safety and efficacy for mass vaccination. In phase 1 the vaccine is tested in a small group of healthy adults who have not been exposed to the disease (~20-100 people); safety is monitored and immune responses are measured. In safety monitoring they look for anticipated adverse events, like redness and swelling at the injection site, fevers, headaches, muscle pain, as well as serious adverse events which are expected to be rare (including allergic reactions). If there are no safety concerns in phase 1, phase 2 commences. Here the number of people in the trial is increased (100s with different states of health and demographics) and the most effective dosage is determined. In phase 3 the vaccine is given to even more people (1000s). Safety and efficacy testing is continued with some people given the vaccine and some given a control/placebo for comparison. Phase 3 data is submitted to and reviewed by regulatory bodies who will approve and license the vaccine for use if the data passes scrutiny.

So how do I decide whether to take it? Mainly based on a good phase 3 safety profile. For example, the Centers for Disease Control (CDC) in the US published a report on Jan. 15 showing that there were 11.1 allergic reactions per a million doses of the Pfizer/BioNTech vaccine administered –so considered safe. One can also look at published results with safety profiles such as that recently published for Sputnik V (Gamaleya Research Institute Vaccine) in the prestigious medical journal, The Lancet.

What about efficacy? Note, the WHO suggested that a “clear demonstration of efficacy (on a population basis)” for any acceptable COVID-19 vaccine is

50% minimum (preferred 70%). Approved Influenza vaccines are usually 40-60% effective. So, if a safe but less effective COVID-19 vaccine is the only vaccine available, I would definitely take it. Something else to note, vaccines are effective against specific variants/strains/ subtypes they target. For example, the Novavax vaccine showed an 89.3% efficacy in a UK clinical trial but this is reduced to 49.4 % in South Africa where there is high prevalence of a new more contagious variant. Moderna and Pfizer/BioNTech vaccines also show lower efficacy against this new variant relative to the original SARS-CoV-2 strain. Phase 3 trials for CoronaVac (Sinovac vaccine) in Turkey and Indonesia, with ongoing mass vaccination campaigns, report it to be 91.2% and 65.3 % effective, respectively. Further, reducing the dose, from that used in clinical trials where efficacy was determined (as that done for the Oxford/AstraZeneca vaccine in the UK), may also alter efficacy.

2. People worry that because these vaccines were developed and tested so quickly, they are not safe

Yes, vaccines were developed quickly but we are at a stage where we have the technological resources to do so. For example, the SARS-CoV-2 genome - vital information for drug and vaccine development - was sequenced and made available on Jan. 10, 2020 less than a month after the WHO was informed of COVID19. For some perspective, scientists were only able to sequence part of the influenza virus genome 79 years later after the deadly 1918 influenza pandemic; they did it with preserved lung tissue from a victim who died in the 1918 pandemic. And, although no RNA vaccines (Pfizer/BioNTech and Moderna type) have been approved until now they have been under development for targeting viruses including influenza, Zika, rabies and HIV. Further, many vaccine researchers have worked on Coronaviruses before, for example, the original Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East respiratory syndrome-related coronavirus (MERS-CoV). So, COVID-19 vaccine research and development did not start from zero but with plenty of foundational science.

In summary, lower efficacy in a vaccine does not translate into it being sub-standard. If it’s safe and passes scrutiny in regulatory review, it’s good for me. Lower efficacy means that more of the population needs to immunized to allow for person-to-person transfer to become highly unlikely (the primary goal of vaccination campaigns). So, this shouldn’t deter you from getting vaccinated. Further, the more people vaccinated means less people out there vulnerable to infection and therefore less opportunity for the virus to spread and mutate into more contagious forms or worse, be able to evade current vaccines. We’re not at that stage as yet. Let’s not let that happen.