Working of vaccines through Immune Correlates of Protection

Vaccines are given to protect against diseases and possibly infection. Protection comprises the various immunological processes involved to reduce the intensity of the disease or infection. When a vaccine is administered, the body recognises it as an infection, since vaccines are antigens that are either a deactivated form or a part of the pathogen. While developing a vaccine, the researchers must refer to a set of possible immune responses that it could elicit when administered to the human body, called Immune Correlates of Protection (ICP). ICPs can also help with understanding the vaccine efficacy. 

According to the vaccine development guidelines provided by CDSCO, ICPs are established on the basis of one or more of the following parameters:

  1. Studying the serum components of the infected individuals in a specific population 
  2. Inducing passive immunity by administering antibodies (obtained from immunized individuals or clinically engineered monoclonal antibodies) 
  3. Efficacy and effectiveness trials
  4. Understanding why vaccines failed in immunocompromised individuals

ICPs should explore all the possible vaccine-induced protective responses in individuals against their own pathogen which can help in comprehending the mechanisms involved. ICPs should include an investigation of the immune status of the infected individual and the microbial load post-recovery. The levels and activity of functional antibodies are the most important component to be considered in an ICP.  A single ICP for a specific vaccine construct may not be applicable to other vaccine constructs. If there are no established ICPs like in the case of understanding the workings of a new candidate vaccine, the elicited immune responses from trials can be correlated with any existing animal models or non-clinical ICPs (should be used with caution). 

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Certain principles should be considered while using or referring to ICPs:

  1. Larger doses of the vaccine can increase the immune response thereby interfering with identifying accurate correlates
  2. The mechanism of protection is not the same as the mechanism of recovery 
  3. Despite functional antibodies being the key protector against infection, other components of the immune system can also be involved in vaccine-induced protection
  4. Antibodies induced through vaccines need not have longevity and can thereby render the individual susceptible to future infection
  5. Correlates vary from one individual to another based on age, gender and genetic predisposition 

Possible ICPs for Infection and Vaccine-Induced protection against COVID-19 virus 

In the case of the SARS-CoV-2 virus, both the infection as well as the vaccine garners a robust immune response. A review paper titled Potential SARS-CoV-2 Immune Correlates of Protection in Infection and Vaccine Immunization” by Sui et al provides an account of all the possible immune correlates for the SARS-CoV-2 vaccines. Identifying and interpreting the ICP for the SARS CoV-2 virus should be approached with extra caution as the information is complicated and can sometimes be misleading. Larger viral loads and higher vaccine doses can elicit a more pronounced immune response conferring long term immunity. Milder or symptomatic forms of the coronavirus infection bring about a lower immune response. 

When infected with the SARS-CoV-2 virus, antibodies of the IgG, IgA and IgM types were observed against the spike protein within two weeks of the infection. These antibodies were also detected in the plasma of convalescent COVID-19 patients. Virus-specific CD4+ T-cells and CD8+ T-cells were also identified in the bloodstream of the infected individuals which targets the glycoprotein moieties of the virus. Although evidence is lacking for the specific protective nature of CD4+ T-cells, it may serve as the key to sustained production of neutralising antibodies. Further studies stated that cell-mediated responses sustained longer (for around 5-6 months) even when the humoral response waned out (within a few weeks). 

When the various types of Covid vaccines were administered to animal models and phase II patients, similar responses to that of naturally infected states were seen with the sera having high values of neutralising antibodies. Virus-specific CD4+ T-cells and CD8+ T-cells were also detected. However, T-cell responses alone do not protect against the virus. Transfer of antibodies from convalescent plasma to healthy individuals can also help in protection against the virus. 

Innate Immunity also plays a huge role in protection against the virus, with type-1 interferons being a necessary factor in protection. Increased cytokine production along with lower type-1 interferon levels have been shown to exacerbate the viral infection. Trained immunity is the increased reactiveness of myeloid cells and natural killer cells when they reencounter other pathogens. Studies conducted by Covian et al have stated that countries that provide the BCG vaccine at a younger age showed a lower rate of Coronavirus infection via trained immunity (10% increase in the BCG vaccination prevalence led to a 10.4% reduction in COVID-19 mortality, Escobar et al). 

Understanding the ICP can help in developing better vaccines in order to help with protection. The need for effective vaccines that provide long term protection against the SARS-CoV-2 virus is crucial due to the high communicable nature of the virus. ICP can also help in understanding some of the possible side effects associated with the vaccine thereby helping its development.

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