The world is eagerly awaiting a vaccine against Covid-19. Research institutions and drug makers across the world are racing to come up with a safe and effective vaccine. Announcements from lead runners have been encouraging. And yet, many questions remain unanswered. The challenge of administering the vaccine to billions of people across the world is daunting. Each country will have to plan well in advance to finance, procure, and organize population-wide vaccination.
The challenge for India, with a population of over 1.3 billion, is huge. India has, in the past, demonstrated its abilities in meeting challenges of this nature, despite its weak health system. India boasts of one of the largest vaccine manufacturing capacities in the world. India boasts of a widespread network of frontline health workers that has been effective in undertaking programs at scale.
A majority of Indian states are witnessing a declining caseload, despite greater unlocking of restrictions. Multiple seroprevalence studies are pointing to a high rate of asymptomatic infections. Studies in a few slum communities have demonstrated very high seroprevalence rate ranging from 30 to 50 percent. These trends point to the phenomenon of natural herd immunity in the setting of continuing preventive measures of using face masks and practicing social distancing and hand hygiene.
The proportion of people required to be evidently immune in order to achieve herd immunity is arrived at by the formula (1-1/R0), where R0 is the reproduction rate of the virus, i.e., number of people one infected person infects. When the desired proportion of the population acquires immunity, the virus fails to spread in the population. It is well established that simple containment measures like face masking, social distancing, and hand hygiene can bring down the R0 value to <1.5 from a high of ~2.5 when no measures are in place. As per the above formula, the proportion of people needed to achieve herd immunity at R0 value of 2.5, 2.0, 1.5, and 1.2 are 60%, 50%, 33.3%, and 16.6% respectively.
Hence, the current decline in numbers should not give rise to a false sense of herd immunity and lead to lowering the guard in terms of containment measures. Until 60 to 70% of the population develops immunity either because of natural infection or because of vaccination, all the containment measures should continue.
Additional caveats are to be kept in mind while coming up with policies and strategies for effective population level vaccination. It is not clear whether those with evidence of prior infection have robust protection against reinfection and if yes, for how long. Recent studies have demonstrated that the antibody levels decrease rapidly in those with no or mild symptoms. The decrease in antibody levels, however, may not equate with a decrease in immune protection against reinfection. This is because the body harbors memory B cells and T cells. Memory B cells can be recruited to start antibody production at a short notice and T cells mount cell mediated immunity against the invading virus. Whether we need to test people for the presence of protective antibodies prior to vaccination is not clear yet.
Vaccination strategies will have to account for the differences in the various vaccines that are in the advanced stage of development. These are different type of vaccines, namely, mRNA, component proteins, viral vector, inactivated virus, and attenuated virus among others. This means there are differences in various factors such as temperature stability, dosage (single versus two doses), ability to induce both humoral (antibody-based) and cell-mediated immunity, the demonstrated duration for which they provide protection, safety profile, and cost among others.
Financing a massive vaccination program at a time when the country is going through great economic hardship is an important policy decision to be considered. Given the narrow fiscal space, policy makers must exercise priority setting. Any policy needs to ensure that the most vulnerable and the most essential people get equitable access to the vaccine without any financial hardships. There is a great risk of policies being influenced by the exigencies of political capital. These need to be curbed. Since health is a state subject, there should be consensus on formulating a national policy, for adoption by each and every State irrespective of their political dispensation.
It is hoped that the government is seized of the matter and is developing robust strategies involving experts across the various spectra of health systems. It requires greatest war-like operational planning in mission mode. India has the will to do it and it can.
Round up of Major Vaccine Candidates and their Current status
Some of the leading Covid-19 vaccine candidates around the world are nearing the end of the phase three of human trials. Phase 3 trials are designed to test the efficacy of the vaccine efficacy before seeking regulatory approval for public use. Globally, AstraZeneca, Pfizer, Sputnik V, and Moderna have revealed encouraging results from their phase 3 trials.
In the Indian context, there are nearly 20 vaccine candidates, either being developed indigenously or in partnership for manufacturing and/or distributing a foreign developed vaccine. Two of India’s homegrown candidates are in the advanced stage of clinical trials. India is also conducting clinical trials for some of the major global vaccine candidates. Vaccine developers in India have begun applying to the central Drugs Standards and Control Organization for Emergency Use Authorization.
Currently, following these are some of the vaccines in the Indian context, most of them in advanced stages of trial.
Covishield is being developed by the University of Oxford and the Anglo-Swedish pharma company AstraZeneca. Pune-based Serum Institute of India (SII), the largest vaccine maker in the world in terms of volume, will be producing this vaccine. The pharma company entered into a licensing agreement with SII for the supply of one billion doses of this vaccine for low and middle-income countries.
SII is currently conducting the third phase of human trials in India and hopes to have 100 million doses of this vaccine by January. The vaccine will be given to patients in two doses. Covishield is being tested in 16,000 volunteers across the country. One trial participant had, in late November, allegedly reported an adverse reaction to this vaccine last month. However, SII said that the reaction was not related to the trial.
The promising results of the trials have made experts believe that Covishield could be a realistic solution to the pandemic and is the leading contender in India. It has shown an efficacy of over 60 percent. Moreover, it is expected that this vaccine will not require ultra-cold storage, making it a practical solution for low and middle income countries.
Developed by Hyderbad-based pharmaceutical company Bharat Biotech along with the Indian Council of Medical Research, Covaxin is India’s first indigenously developed Covid-19 vaccine. Phase-three of the human clinical trial of Covaxin is currently underway at 25 hospitals across the country with over 25,000 participants. No data about the efficacy of this vaccine has been made public yet. However, it is expected that the vaccine will be 60% effective. Bharat Biotech has a limited capacity to produce the vaccine at present, but it expects to scale up its capacity to produce a billion doses to be able to launch it in mid-2021.
Developed by Ahmedabad based pharma company – Zydus Cadila, the ZyCOV-D is currently under phase 3 of trials, which began recently with close to 30,000 participants. Zydus Cadila had announced earlier that the phase-I trial was over and had commenced phase-II clinical trials from August. The results from the ongoing phase 3 of the trial are likely to be available early next year. Unlike Covaxin and Covishield, ZyCov-d will be a three-dose Covid-19 vaccine.
The Sputnik V, developed by Russia’s Gamaleya Research Institute of Epidemiology and Microbiology has partnered with in Hyderabad-based pharmaceutical company Dr Reddy’s. The Indian drugmaker and the Russian Direct Investment Fund (RDIF) entered into an agreement in September to conduct trials in India. The phase III trials began in India on December 1 with 40,000 participants. If successful, Dr Reddy’s will also have distribution rights for 100 million doses for India. The RDIF expects the vaccine to be available next month.
Serum Insititute of India is also developing the Covovax vaccine in partnership with US-based biotech company Novavax. While the third phase of the trial has been delayed, Novovax’s collaboration with SII has enabled it to produce up to two billion doses of its vaccine a year, beginning mid next year. Novavax has initiated its late phase trials in South Africa and in the UK and will soon commence the same in the US. The ICMR and SII have collaborated for the clinical development of Covovax developed by Novavax, US and upscaled by SII.
Other Global candidates:
Leading candidates globally with impressive efficacy data based on phase three clinical trials have started applying for emergency use authorization. The final analysis of phase 3 trial data of Pfizer-BioNTech vaccine candidate has found it 95 percent effective in preventing COVID-19 infections. The vaccine candidate consists of two shots administered at an interval of 21 days. One of the major challenges of the Pfizer-BioNTech vaccine candidate is the requirement of special storage equipment and transportation. Britain recently approved Pfizer’s COVID-19 vaccine to become the West’s first country to formally endorse a vaccine.
The preliminary analysis of phase 3 clinical trial data of US based Moderna’s vaccine candidate has found that it was over 94% effective in preventing COVID-19 infections. The vaccine candidate consists of two injections that must be administered at an interval of 28 days. Like the Pfizer-BioNtech vaccine candidate, it has been developed using the mRNA technology. Johnson and Johnson’s COVID-19 vaccine candidate is currently in phase 3 human trials. J&J is researching the viability of both a single-dose as well as two-dose vaccines.
The Challenge of Cold Storage Logistics
Many of the major vaccine candidates require storage at very low temperatures. The temperature factor is an important one for countries like India, where issues such as frequent power cuts and lack of freezers make distribution challenging, especially in rural areas. The Union health ministry has said that mass immunisation will require substantial increase in the number of cold-chain points and equipment such as reefer vans, coolers, and deep freezers.
A research by German logistics firm DHL and consultancy firm McKinsey has found that inadequate last mile cold storage facilities at clinics in large parts of Africa, Asia and South America would pose a big challenge to delivering these vaccines at scale.
The Pfizer vaccine is based on the mRNA technology and has a storage requirement of minus 94 degrees Fahrenheit and can be stored in a regular refrigerator for 5 days. The Moderna vaccine however shows to remain stable at 36 to 46 degrees Fahrenheit and can be stored in a standard refrigerator for nearly 30 days. The Johnson and Johnson vaccine can also be stored at standard refrigeration temperatures. Despite higher efficacy rates of Moderna’s and Pfizer’s vaccine candidates, the AstraZeneca vaccine had been considered a more important candidate due to the lack of requirement of freezers.
The Union health ministry said recently that the cold-chain requirements of the vaccine developed by Pfizer posed a big challenge for India but the government is exploring all possibilities for its procurement.
Developing a safe and effective vaccine against COVID-19 is the most pressing challenge today. It is however important to note that it is not about who is able to successfully develop this vaccine first.The pandemic will not end until a significant portion of the global population is vaccinated and this would not be possible without equitable access to a vaccine. For this, global cooperation is an absolute must.