Since the very beginning of the outbreak of the novel SARS-CoV-2, pharmaceutical companies from around the world have been racing against not only time, but against each other, as well, to be the first to manufacture an approved vaccine for the coronavirus. Companies have taken many different approaches to this, including protein subunit vaccines, RNA vaccines, whole virions, non-replicating viral vectors, etc. If it can be used to develop a vaccine, you can bet the option has been or currently is being explored. One of the big name companies participating in this vaccine race is Bharat Biotech of India. According to their website, Bharat Biotech is a world-class biotechnology company with a mission to deliver safe, affordable, and high quality vaccines to people and have a focus on emerging markets, such as the market created by recent the SARS-CoV-2 outbreak.
If you navigate to their vaccine section of their website, you can see that Bharat Biotech has recently been approved to begin Phase 3 clinical human trials after successful interim analysis of their Phase 1 & 2 trials for their newly manufactured vaccine, COVAXIN. According to this informational webpage released by the FDA, Phase 1 trials typically last several months and enroll anywhere from 20-100 individuals to participate. The main focus of this phase of the trial is to establish a safe dosage and the effectiveness of a safe dosage of the vaccine. If the study passes Phase 1 of clinical trials, it may proceed to Phase 2 (about 70% of studies are approved to progress). Phase 2 of clinical trials can last anywhere from months to two years, and can enroll several hundred people in the study. The main purpose of this portion of the study is to determine efficacy and side effects in patients. Typically, only about 33% of vaccines or drugs will progress past this stage. Phase 3 of clinical trials can last anywhere from a year to four years, and enrolls anywhere from several hundred to several thousand participants. COVAXIN is, as previously mentioned, beginning Phase 3 of clinical trials and was actually approved for the enrollment of 26,00 participants across 25 centers in India. This phase has an emphasis on the monitoring of adverse reactions to the drug. The fourth and final stage of clinical trials focuses on, once again, the safety and efficacy of the drug/vaccine and is eligible to enroll thousands of participants.
While their website offers little information on the science behind the vaccine, the CDC has released a document summarizing many of the key components of vaccines in the running, including COVAXIN. COVAXIN is an inactivated whole agent vaccine. This means that the vaccine contains whole organisms (viruses) that have been inactivated by treating the pathogen with a chemical that kills the organism without significantly altering the surface epitopes. Essentially, the antigen is capable of remaining immunogenic through the epitopes, but is incapable of reproducing. The inactivated organism is injected into the patient and elicits an immune response that creates antibodies and memory cells against the pathogen, in this case SARS-CoV-2, but the virus is unable to replicate, so the immune response will not be overpowered by the invading organism. This allows the patient to build up active immunity to the antigen so that when the live virus is encountered later in life, the body already has made a primary immunogenic response and can use that to generate a much more effective and stronger secondary response when encountered in vivo. Since COVAXIN is an inactivated vaccine, it will require 2 doses to elicit a response large enough for the body to maintain an immunogenic response (booster shot). The second vaccine is proposed to be given 14 days after the initial vaccine.
No information that I have encountered addresses the nature of the study used to determine the effectiveness of COVAXIN, but many human clinical trials, including many (I imagine) exploring COVID-19, utilize a double blind placebo study design, In this study design, there are two (at least) groups of patients treatment. One of those is typically the experimental drug group, and the other is a placebo group. A placebo is a substance that has no medicinal effect (like a sugar pill or inactive ingredients) that can be used to compare whether or not the experimental drug really shows any significant difference in prevention. The placebo is harmless and usually has no effect, good or bad, on the patients physical health. Mentally, the placebo could elicit the placebo effect, which can be confounding but is less of a concern in preventative drug studies due to the objective nature of the results. In this study design, participants are “blindly” assigned to either the experimental or placebo/control group, meaning they don’t know which group they are in. Likewise, the researcher administering the vaccine is also “blind” in that they are also unaware of which patients are receiving the real vaccine versus the placebo. This is an extremely effective study design because it greatly diminishes any bias that could impact the findings of the studies.
Another topic of discussion regarding vaccines is that of the speculation of companies potentially requesting an Emergency Use Authorization (EUA) for their naive vaccines. As noted by this Wikipedia page on EUAs, n EUA allows the FDA to facilitate availability of the unapproved vaccine during a declared state of emergency. This would allow companies hand out their vaccine during states of emergencies while the product remains unapproved. This could cause chaos in the testing process because an the efficacy standards of the vaccine may be compromised under the circumstances. In other words, the companies may begin to release a vaccine that is “maybe effective” under the EUA since it is an emergency; however, any vaccine attempting to gain FDA approval should have higher efficacy standards than “maybe.” EUAs may also speed along the research portion of the vaccine clinical trials, which may result in an increased risk of error in approval of a substance that might not yet be ready for approval.