Even though the World Health Organization (WHO) no longer defines COVID-19 as a Public Health Emergency of International Concern (PHEIC), it continues to take a significant toll on health globally. With the pandemic now in its fourth year, it is clear the virus is likely to stay with us for many years to come – if not forever1. Meanwhile, the SARS-CoV-2 virus that causes COVID-19 continues to mutate to form new variants and subvariants. Vaccines have been developed and administered to billions of people. The first version of the vaccines made by Moderna/Lonza and Pfizer/BioNTech targeted the spike (S) protein on the original version of the SARS-CoV-2 virus. This S protein is an antigen that stimulates the production of antibodies when the virus infects the body. That is, the SARS-CoV-2 virus structure has many copies of a protein on its surface that looks like a spike.

The vaccines contain messenger RNA (mRNA) that codes for the S protein. The mRNA is translated into the S protein. By itself, the S protein is harmless and can’t cause COVID-19. However, it does cause the human immune system to develop antibodies that target the S protein when it is attached to an intact SARS-CoV-2 virus. These antibodies bind to the virus and trigger the human immune system to destroy it. At the same time, memory cells are produced so our immune system can recognize future infections. When a person is vaccinated, the viral S protein enters the blood. The innate immune system detects it and activates the acquired immune system, producing a long-lasting immunity. So, when an immunized person is exposed to the virus from an infected person, his or her immune system will destroy the virus once it enters the bloodstream.

That is, we have both an innate and an adaptive immune system. The human immune system has a fast initial response to infection that is innate and needs no training. Similar innate immune systems exist in all animals. There is a cell-based innate immunity that consists of white blood cells (also known as leukocytes) and a variety of biochemicals in body fluids, formerly called humors. The three types of leukocytes are granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes (T-cells and B-cells). Infected cells are killed by phagocytosis using a subgroup of leukocytes that circulate in the bloodstream as monocytes. They are converted into macrophages, which subsequently enter tissues during inflammation. So, one’s innate immune system can often destroy invading viruses, even if one is not vaccinated or previously exposed to the virus.

Vertebrates also have an acquired immunity that provides a slower but sustainable response. This acquired or adaptive immune system produces immune cells that have memory. They can remember the S protein and other antigenic proteins that viruses, bacteria, and other deadly organisms can produce when they infect a person. These immune cells are made in the bone marrow (B-cells) and thymus (T-cells). Most B-cells are distributed in tissues throughout the body, including the lymph nodes, as are T-cells. A smaller fraction of B-cells circulates through the blood vessels. Activated B-cells are cleared in the liver and spleen, so they only survive a few days. Naïve B-cells, which have not been exposed to antigens and memory B-cells, are protected and live much longer. When a person with a healthy immune system is infected by a virus, bacteria, or pathogenic organism, some of the B cells produce antibodies that may persist for months or years. So, pathogen-specific B cells persist in a resting state. They circulate in the body and can be reactivated to produce more antibodies when a person is infected again. However, these two types of B cells produce different antibodies. The class, or isotype, usually changes. It is no longer the IgM class that was initially produced. The affinity of the antibody for the pathogenic antigen is much stronger than in the initial immune response. The immune memory includes not just the antibody that is made but also the B-cells and T-cells that combine rapidly to make more antibodies. This repeats and magnifies the previously successful immune responses. Different classes of antibodies appear in the memory compartments. They are specialized in clearing specific types of pathogens.

However, the SARS-CoV-2 virus has mutated into different forms, or variants. Some of them have caused much concern in the medical community. These are known as variants of concern (VOC). The WHO defines a VOC as a variant that has been demonstrated to be associated with one or more of the following changes2:

  • Increase in transmissibility or detrimental change in COVID-19 epidemiology; or,
  • Increase in virulence or change in clinical disease presentation; or,
  • Decrease in effectiveness of public health and social measures or available diagnostics, vaccines, and therapeutics.

The Centers for Disease Control (CDC) in the USA have a slightly different definition 3. To them, a VOC is a variant for which there is evidence of an increase in transmissibility, more severe disease (such as increased hospitalizations or deaths), a significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.

The different VOCs have been named in accordance with the Greek alphabet. The first five VOCs designated by the WHO were called Alpha, Beta, Gamma, Delta, and Epsilon. The Delta variant was dominant for many months but was overcome by the Omicron variant. On November 25, 2021, the African Union and Africa Centers for Disease Control and Prevention released a statement that identified the newest VOC, the omicron variant, also known as the B.1.1.529 variant4. This variant has over 30 mutations in the part of the mRNA that codes for the spike protein. This is because the antigen used by Moderna and Pfizer/BioNTech mRNA vaccines to train one’s immune system to recognize and eliminate the SARS-CoV-2 virus has changed. Just one month after its discovery, the Omicron variant has been transmitted more efficiently, impacted vaccine effectiveness, and evaded immune responses in many people. However, it usually causes less severe symptoms and a milder disease.

So, subsequent versions of the Moderna/Lonza and Pfizer/BioNTech vaccines were prepared that target not only the original version of the SARS-CoV-2 virus but also the omicron variant that was first identified almost two years ago. These were called bivalent vaccines because they targeted two versions (or variants) of the virus. They were administered to billions of people worldwide. However, they were not as effective in preventing infection by the most recent subvariant of omicron. This subvariant (known as XBB.1.5) has become the predominant form of the SARS-CoV-2 virus. So, Moderna and Pfizer/BioNTech have developed vaccines that target the S protein on the XBB.1.5 subvariant5-6. Clinical trials showed that the updated vaccine is effective against the variants that are currently causing most of the cases of COVID-19 in the USA. These vaccines have been approved by the Food and Drug Administration (FDA) in the USA and are recommended by the CDC. They are the only COVID-19 vaccines that are available this season. With the updated COVID-19 vaccines, we're back to what is called a monovalent vaccine, meaning there's only one component compared with the previous bivalent vaccines.

The CDC recommends that everyone 6 months of age or older get a new COVID-19 monovalent vaccine targeting the Omicron subvariant XBB.1.5. The CDC’s move came the day after the FDA approved Moderna’s and Pfizer-BioNTech’s updated COVID-19 messenger RNA (mRNA) vaccines for people 12 years of age or older and authorized the shots for emergency use in children 6 months through 11 years of age. For individuals 5 years and older, one dose of the updated Pfizer-BioNTech or Moderna COVID-19 vaccine is recommended. According to updated CDC guidelines, people in certain risk groups may want to receive more doses with their health care provider’s guidance. For children ages 6 months to 5 years, vaccination is recommended, but the number of vaccinations is based on which vaccine (Pfizer-BioNTech or Moderna) they receive, as well as their age. People at a higher risk of severe illness should get an updated COVID vaccine as soon as possible. With the holiday season ahead of us and cooler weather driving more indoor gatherings, experts recommend that everyone who is eligible get their updated COVID vaccine by mid-October.

There is also an updated Novavax COVID-19 vaccine that is authorized for people 12 years of age and older. Unlike Pfizer-BioNTech and Moderna’s vaccines, the Novavax vaccine uses the S protein instead of an mRNA. So, it’s an option people can consider if they are unable or choose not to get an mRNA vaccine.

So, millions of people have already received one of these new vaccines. Even though there is still a possibility that vaccinated people can still be infected by the virus, they are almost all going to be protected against developing the most severe symptoms of COVID-19, including hospitalization and death. However, we are not machines. We are not all going to react to the vaccine for the disease the same way. People who are immunocompromised might be advised not to get these vaccines. That decision should be made under the guidance of a physician.


1 World Health Organization. With the international public health emergency ending, WHO/Europe launches its transition plan for COVID-19. 12 June, 2023.
2 World Health Organization. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. 26 November 2021.
3 Centers for Disease Control, CDC. SARS-CoV-2 Variant Classifications and Definitions. 23 June, 2021.
4 African Union, Africa Centres for Disease Control and Prevention’s statement regarding the new SARS-COV-2 virus variant B.1.1.529, 25 Nov., 2021.
5 Rubin, R. Updated COVID-19 Vaccine Now Available in US, Recommended for Everyone Older Than 6 Months. Jornal of the American Medical Association, 2023.
6 Mahase, E. Covid-19: What do we know about XBB. 1.5 and should we be worried?, British Medical Journal, article 380, 2023.