Covid-19 vaccines: what should we know? |06 January 2021

The world is fighting the Covid-19 pandemic and Seychelles started 2021 with some cluster community transmission. Many countries are still imposing lockdown in order to break the chain of transmission although they have the vaccines. The World Health Organisation has confirmed more than 50 Covid-19 vaccine candidates in trials.

In Seychelles we do have the vaccine Sinopharm and an online poll shows that many people are reluctant to take the vaccines. In order to inform ourselves more on how vaccines work we propose to our readers the following research work from the International Vaccine Access Center from Johns Hopkins University & Medicine.

How do vaccines work?

Vaccines stimulate the human body’s own protective immune responses so that, if a person is infected with a pathogen, the immune system can quickly prevent the infection from spreading within the body and causing disease. In this way, vaccines mimic natural infection but without actually causing the person to become sick.

For SARS-CoV-2, antibodies that bind to and block the spike protein on the virus’s surface are thought to be most important for protection from disease because the spike protein is what attaches to human cells, allowing the virus to enter our cells. Blocking this entrance prevents infection.

Not all people who are infected with SARS-CoV-2 develop disease (Covid-19 is the disease caused by the virus SARS-CoV-2). These people have asymptomatic infection but can still transmit the virus to others. Most vaccines do not completely prevent infection but do prevent the infection from spreading within the body and from causing disease. Many vaccines can also prevent transmission, potentially leading to herd protection whereby unvaccinated people are protected from infection by the vaccinated people around them because they have less chance of exposure to the virus.

What are the different types of vaccines in development and why are there so many?

Several different types of vaccines against SARS-CoV-2, the virus that causes the disease Covid-19, are in development. Some are based on traditional methods for producing vaccines and others on newer methods. One of the more traditional ways of making a viral vaccine is to inactivate (kill) the virus with chemicals, such as is done with the flu vaccine, inactivated polio or hepatitis A vaccines, so that the virus can no longer multiply. Several inactivated SARS-CoV-2 vaccines are in development. Other vaccines are based on just a part of the bacteria or virus, typically one or more proteins, such as the vaccines for whooping cough (pertussis) and hepatitis B virus. For SARS-CoV-2 vaccines that focus on a part of the virus, this often means the spike protein on the surface of the virus.

Newer vaccine types include what are called viral vector vaccines, in which the SARS-CoV-2 gene for the spike protein is inserted into another harmless virus to deliver the gene to human cells where the spike protein is produced. The spike protein then stimulates immune responses. The most common viral vectors are adenoviruses, which typically cause common cold-like symptoms in people but are further weakened for vaccines so they cannot cause any disease at all. Several adenovirus vector vaccines for SARS-CoV-2 are in advanced clinical testing (phase 3 clinical trials).

Finally, instead of using a viral vector, the gene for the spike protein can be used directly as a vaccine in the form of DNA or messenger RNA (mRNA). These are the most novel SARS-CoV-2 vaccines. Several mRNA vaccines are in advanced clinical testing.

Many manufacturers around the world are working on this global problem. This means that there will likely be multiple different types of SARS-CoV-2 vaccines and they may work differently in different people. Hopefully, some will work well in older adults and in people with underlying conditions that impair their immune system, as these groups are more likely to get sick and die from Covid-19.

How will we know if a vaccine is safe and effective?

The safety and efficacy of a vaccine is determined through clinical trials. Clinical trials are studies that are typically conducted in three phases to assess the safety and efficacy of vaccines in increasingly larger numbers of volunteers.

Phase 1 clinical trials assess the safety and dosage of a vaccine in a small number of people, typically a dozen to several dozen healthy volunteers. Whether a vaccine stimulates immune responses is often assessed in a phase 1 study but this is better assessed in phase 2 studies, which typically involve hundreds of people including some special groups such as children, people with pre-existing conditions such as heart disease, and older adults. Vaccine safety is also assessed in phase 2 studies, in which adverse events not detected in phase 1 trials may be identified because a larger and more diverse group of people receive the vaccine. However, only in much larger phase 3 clinical trials can it be demonstrated whether a vaccine is actually protective against disease and safety is more fully assessed.

Phase 3 clinical trials often include thousands of volunteers, and for Covid-19 vaccines will involve tens of thousands (30,000 to 45,000 people in some of the ongoing phase 3 trials). In phase 3 trials, participants are randomized to receive either the viral vaccine or a placebo vaccine (sometimes a vaccine against another disease or a harmless substance like saline). Randomization is a process to determine who receives the vaccine and who receives the placebo without any bias, like flipping a coin. To further prevent any bias in interpreting the study data, participants and most of the investigators will not know if an individual received the vaccine or placebo. The participants are then followed to see how many in each group get the disease. If the vaccine is efficacious, many fewer people who received the viral vaccine will get the disease compared to those who received the placebo vaccine. It takes time for cases of disease to accumulate so that we can be confident there is a true difference between the two groups, and this is why these phase 3 trials often take a long time. Assessing safety is also a major goal of phase 3 trials, both short-term safety (e.g. fever, tenderness, muscle aches) and long-term safety (e.g. autoimmune conditions or enhanced disease following infection).

After a vaccine is approved and in more widespread use, it is critically important to continue to monitor for both safety and effectiveness. Some very rare side effects may only be detectable when large numbers of people have been vaccinated. Safety concerns that are discovered at this late stage could lead a licensed vaccine to be withdrawn from use, although this is very rare.

When will a vaccine be available?

Vaccines for SARS-CoV-2 will be available when they are demonstrated to be safe and efficacious in large phase 3 clinical trials, have been approved by regulatory authorities (the Food and Drug Administration in the United States), and have been manufactured and distributed to places where people can be vaccinated.

To demonstrate efficacy, sufficient differences in disease must be observed between those who received the viral vaccine and those who received the placebo or comparison vaccine in a phase 3 clinical trial. This depends on the likelihood of infection in places where the studies are conducted but can take from several months to years. Once sufficient data are available to be confident that the vaccine is efficacious, and no evidence of serious adverse events is identified, a rigorous and transparent approval process should take place.

Manufacturing capacity has already been developed for some vaccines and vaccine distribution systems are being put in place. However, because of limited quantities of vaccine, some groups of people will be offered the vaccine first, likely health care workers, other essential personnel, and those most vulnerable to severe disease and death.

How is the process for approving a vaccine moving so quickly?

Traditionally, it has taken many years to develop a vaccine, confirm its safety and efficacy, and manufacture the vaccine in sufficient quantities for public use. This timeline is substantially shortened for SARS-CoV-2 vaccines in development. There are several ways this has been made possible. First, some clinical trials have combined phases 1 and 2 to assess safety and the immune responses. Second, because of the high number of new cases of Covid-19 in many places, differences in disease risk between those who received the viral vaccine and those who received the placebo or comparison vaccine can be measured more quickly than in the absence of a pandemic. Third, the United States government and others have heavily invested in building the manufacturing capacity to produce large numbers of vaccine doses before the findings of the phase 3 trials are available. Typically, vaccine manufacturers wait until the phase 3 trial is completed and shows safety and efficacy before making such a large investment in manufacturing capacity. None of these factors that contribute to the accelerated development of a vaccine for SARS-CoV-2 imply that safety, scientific or ethical integrity are compromised, or that short-cuts have been made.

What is an emergency use authorisation?

Drugs and vaccines have to be approved by the Food and Drug Administration (FDA) to ensure that only safe and effective products are available to the American public. In situations when there is good scientific reason to believe that a drug is safe and is likely to treat or prevent disease, the FDA may authorise its use even if definitive proof of the efficacy of the drug is not known, especially for diseases that cause high mortality.

Emergency use authorisations were granted by the FDA Commissioner for chloroquine and hydroxychloroquine (later revoked) and for the use of convalescent plasma to treat hospitalised patients with Covid-19. Many are concerned that Emergency Use Authorisation for a vaccine could be issued prematurely, before sufficient safety and efficacy data have been generated through phase 3 clinical trials.

It is important to emphasise that the bar for ensuring safety of a vaccine is higher than for a therapeutic to treat an ill person. Vaccines are given to potentially millions of healthy people, unlike drugs for sick people, and loss of trust in a vaccine for SARS-CoV-2 could spill over into loss of trust in other vaccines, seriously jeopardising public health.

How long will it take for the general public to be vaccinated after a vaccine is approved?

It is not clear at this point in time when a vaccine for the general public will be available, but a reasonable guess may be at least six months to one year after approval. The timeline depends on how rapidly vaccine doses can be produced and distributed. Importantly, the public will need to trust a vaccine and be willing to be vaccinated to have a public health impact. Building trust in a vaccine for SARS-CoV-2, particularly in communities with long-standing mistrust of the government and scientific experiments, is critical.

Should children get the vaccine?

Children will not be a priority group for a vaccine early in vaccine deployment but will likely be eligible as vaccine availability improves. The major vaccine clinical trials are currently focused on enrolling adults, and as they expand, the inclusion of children in vaccine clinical trials will produce data on safety and efficacy that can be applied to children. While children are less likely to develop severe disease and die from Covid-19, there are several reasons for ensuring that eventually there is a vaccine that is safe for children. Although rare, some children may develop severe disease or die from Covid-19. Children have also developed a severe inflammatory syndrome, called multisystem inflammatory syndrome in children. Children may be important transmitters of SARS-CoV-2 and vaccinating them with a vaccine that reduces transmission could be important in controlling the pandemic. Finally, having a safe vaccine for children will build confidence towards opening up schools and learning centres for in-person educational processes.

How long will protection last following vaccination?

We do not know how long protection will last following vaccination but it will be critically important to measure long-term protection (at least two years) in the phase 3 trials and in other groups prioritized for early vaccination. We are still learning about the duration of protection following infection with SARS-CoV-2 and it is too early to tell how long protection will last. There have already been cases where individuals have been shown to be infected twice but most often the second illness was mild or without any symptoms. This is what we would expect with an immune response that protects against disease but not infection.

There are ways to potentially make protection following vaccination more durable than following natural infection, such as with an adjuvant, an ingredient used in some vaccines that helps create a stronger immune response, or with booster doses of vaccine. These strategies to enhance vaccines may be particularly important for vulnerable populations, such as the elderly and those with underlying diseases, who are at particular risk of severe Covid-19 but are also less likely to develop a protective immune response to a vaccine.

If I already had Covid-19, should I still get a vaccine?

When people recover from some viral infections, such as measles or mumps, they are protected against reinfection and would not need to be vaccinated. However, for other diseases, such as pneumococcal pneumonia or influenza, it is important to be vaccinated (or revaccinated) despite having disease because the vaccine protects against several strains or types of the pathogen and thus can still be valuable. There is no evidence that there are significant differences in SARS-CoV-2 to warrant vaccination for this reason, but we do not yet know how long people are protected after having Covid-19 and so do not yet know if these people should be vaccinated. If protection only lasts for several months, vaccination could be of benefit.

Can someone get Covid-19 from the vaccine?

No, it is not possible to get Covid-19 from vaccines. Vaccines against SARS-CoV-2 use inactivated virus, parts of the virus (e.g. the spike protein), or a gene from the virus. None of these can cause Covid-19.

Will we still need to wear masks and practice physical distancing once a vaccine is available?

We will still need to wear masks and practice physical distancing until a large proportion of the population is vaccinated and we are sure the vaccine provides long-term protection. Initially, we will not have enough vaccine to vaccinate everyone who wants the vaccine and the virus will still be transmitted.

Although the phase 3 clinical trials are designed to determine whether vaccinated individuals are protected against disease, it will also be important to understand whether vaccinated individuals are less likely to transmit the virus. This is likely but not ensured. If a vaccine not only protects against disease but reduces transmission, and continues to do so for many years, we are likely to reach a state of herd protection when masks and physical distancing will no longer be required. Herd protection is achieved when a sufficient proportion of the population is made non-infectious through vaccination or natural infection so that the likelihood of an infectious individual transmitting to a susceptible individual is very low.

Source: https://coronavirus.jhu.edu/vaccines/vaccines-faq