Vaccine and Immunology

Context: The government had decided to open up vaccinations to those above the age of 18 years, and to allow manufacturers to release around 50 % of doses to the open market. 

Relevance: GS-II: Issues relating to development and management of Social Sector/Services relating to Health, Education, Human Resources.

Introduction:

• A vaccine is a biological substance that provides active acquired immunity against a specific infectious disease. A vaccine usually contains an agent that looks like a disease-causing microorganism and is produced from weakened or destroyed microbes, their toxins, or one of their surface proteins.
• The agent activates the body's immune system to identify and kill the agent as a threat, as well as any associated microorganisms it might encounter in the future.
• Vaccines can be either prophylactic (to prevent or mitigate the effects of potential infection by a natural or “wild” pathogen) or preventive (to treat an existing infection) (to fight a disease that has already occurred, such as cancer).

Efficacy:

• Vaccination is the most successful means of combating infectious diseases; vaccination-induced universal immunity is primarily responsible for the worldwide eradication of smallpox and the restriction of diseases like polio, measles, and tetanus in much of the world.
• Vaccine efficacy has been extensively researched and verified; for example, the influenza vaccine, the HPV vaccine, and the chickenpox vaccine have all been shown to be efficient. 
• According to the World Health Organization (WHO), approved vaccines are currently available for twenty-five different diseases that can be prevented.
• Vaccines are a very secure and reliable way to combat and prevent infectious diseases, according to overwhelming scientific consensus. Vaccine agents are recognized by the immune system as foreign, and they are destroyed and “remembered.”
• When a virulent form of a virus is encountered, the body recognizes the virus's protein coat and is ready to react by neutralizing the target agent before it can reach cells, and then identifying and killing infected cells before the agent can replicate in large numbers.
• Nonetheless, there are limitations to their efficacy. Vaccine-related failures, such as failures in vaccine attenuation, vaccination regimes, or administration, or host-related failure, in which the host's immune system simply does not react adequately or at all, can cause safety to fail.
• Genetics, immune status, age, fitness, and nutritional status are all factors that contribute to a lack of response. It may also fail due to genetic reasons if the host's immune system lacks B cell strains capable of producing antibodies that are efficient at responding to and binding to pathogen antigens.

The efficacy or performance of the vaccine is dependent on a number of factors:

1. the disease itself (for some diseases vaccination performs better than for others)
2. the strain of vaccine (some vaccines are specific to, or at least most effective against, particular strains of the disease).
3. whether the vaccination schedule has been properly observed.
4. idiosyncratic response to vaccination; some individuals are “non-responders” to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly.
5. assorted factors such as ethnicity, age, or genetic predisposition.

The following are important considerations in the effectiveness of a vaccination program:

1. careful modelling to anticipate the effect that an immunization campaign will have on the epidemiology of the disease in the medium to long term.
2. ongoing surveillance for the relevant disease following the introduction of a new vaccine.
3. maintenance of high immunization rates, even when a disease has become rare.

• Vaccines led to the eradication of smallpox, one of the most contagious and deadly diseases in humans.
• Other diseases such as rubella, polio, measles, mumps, chickenpox, and typhoid are nowhere near as common as they were a hundred years ago thanks to widespread vaccination programs.
• As long as the vast majority of people are vaccinated, it is much more difficult for an outbreak of disease to occur, let alone spread. This effect is called herd immunity.
• Polio, which is transmitted only among humans, is targeted by an extensive eradication campaign that has seen endemic polio restricted to only parts of three countries (Afghanistan, Nigeria, and Pakistan).
• However, the difficulty of reaching all children as well as cultural misunderstandings have caused the anticipated eradication date to be missed several times.

Negative impacts:

• Vaccines for infants, teenagers, and adults are usually considered healthy. In general, negative impacts, if any, are mild.
• The rate of adverse events depends on the respective vaccine. Some common side effects include fever, site pain, and muscle aches.
• Some people may also be allergic to vaccine ingredients. Febrile seizures are rarely related to the MMR vaccine.

Types of Vaccines:

• Dead or inactivated cells, or purified products derived from them, are commonly found in vaccines.
• Vaccines come in a variety of shapes and sizes. There are various approaches to reducing the risk of infection while maintaining the potential to elicit a beneficial immune response.
• Inactivated: Some vaccines contain previously virulent microorganisms that have been rendered inactive by chemicals, heat, or radiation. The IPV polio vaccine, hepatitis A vaccine, rabies vaccine, and most influenza vaccines are all examples.
• Attenuated: Live, attenuated microorganisms are used in some vaccines. Many of these are live viruses that have been cultivated in conditions that have rendered their virulent properties inactive, or that use closely related but less dangerous organisms to elicit a broad immune response. Although most attenuated vaccines are viral in nature, some are bacterial. Yellow fever, measles, mumps, and rubella are examples of viral diseases, as is typhoid, a bacterial disease.
• Viral vector: Viral vector vaccines use a safe virus to insert pathogen genes in the body to produce specific antigens, such as surface proteins, to stimulate an immune response.
• Toxoid: Toxoid vaccines are made from inactivated toxic compounds that cause illness rather than micro-organism. Examples of toxoid-based vaccines include tetanus and diphtheria. Toxoid vaccines are known for their efficacy.
• Subunit: Rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a “whole-agent” vaccine), a subunit vaccine uses a fragment of it to create an immune response. One example is the subunit vaccine against hepatitis B, which is composed of only the surface proteins of the virus (previously extracted from the blood serum of chronically infected patients but now produced by recombination of the viral genes into yeast).
• Conjugate: Certain bacteria have a polysaccharide outer coat that is poorly immunogenic. By linking these outer coats to proteins (e.g., toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen.
• Heterotypic: Heterologous vaccines are also known as “Jennerian vaccines”, are vaccines that are pathogens of other animals that either does not cause disease or cause mild disease in the organism being treated. The classic example is Jenner's use of cowpox to protect against smallpox. A current example is the use of BCG vaccine made from Mycobacterium bovis to protect against tuberculosis.

Role of World Health Organisation

• Vaccines developed for multinational distribution via the United Nations Children's Fund (UNICEF) require pre-qualification by the WHO to ensure international standards of quality, safety, immunogenicity, and efficacy for adoption by numerous countries.
• The process requires manufacturing consistency at WHO-contracted laboratories following Good Manufacturing Practice (GMP). When UN agencies are involved in vaccine licensure, individual nations collaborate by
  1. issuing marketing authorization and a national license for the vaccine, its manufacturers, and distribution partners; and
  2. conducting postmarketing surveillance, including records for adverse events after the vaccination program. The WHO works with national agencies to monitor inspections of manufacturing facilities and distributors for compliance with GMP and regulatory oversight.

Coronavirus: 

• Coronaviruses are a family of RNA viruses that cause disease in mammals and birds. They cause respiratory tract infections in humans and birds that can range from mild to fatal.
• Mild illnesses in humans include the common cold (which is also caused by other viruses, primarily rhinoviruses), whereas more lethal strains can cause SARS, MERS, and COVID-19. They cause diarrhoea in cows and pigs, but hepatitis and encephalomyelitis in mice.
• The earliest reports of coronavirus infection in animals occurred in the late 1920s when an acute respiratory infection of domesticated chickens emerged in North America.
• Human coronaviruses were discovered in the 1960s in the United Kingdom and the United States.
• Structure: Coronaviruses are large, roughly spherical particles with unique surface projections. Their size is highly variable with average diameters of 80 to 120 nm. Extreme sizes are known from 50 to 200 nm in diameter.

• Replication cycle: All viruses – including SARS-CoV-2, the virus that causes COVID-19 – evolve over time. When a virus replicates or makes copies of itself, it sometimes changes a little bit, which is normal for a virus. These changes are called “mutations”. A virus with one or more new mutations is referred to as a “variant” of the original virus.

SARS-CoV-2 VOI (variants of interest)

Around the world, cases of infection with new variants of the coronavirus SARS-CoV-2 have been rising. Three of them are of particular concern and were first detected respectively in the UK, South Africa, and Brazil.

• A SARS-CoV-2 isolate is a VOI if:
  • It is phenotypically changed (it has a different structure and properties) compared to a reference isolate, or has a genome with mutations that lead to amino acid changes associated with phenotypic implications; and 
  • It has been known to cause community transmission/multiple Covid-19 cases or has been detected in multiple countries.
• UK Variant
  • It is known as B.1.1.7 or VOC 202012/01, it first emerged in the UK last December.
  • In the B.1.1.7 variant are multiple mutations in the spike protein.
  • One mutation, called N501Y, makes the variant more effective at binding to the ACE2 receptor (the human protein that serves as the entry point for the coronavirus).
  • Other significant spike protein mutations are D614G, A570D, P681H, H69/V70 deletion, and Y144 deletion.
• South Africa Variant
  • First detected in South Africa last October, it is called 501Y.V2 or B1.351.
  • This one is defined by nine changes in the spike protein in comparison to the reference — the “Wuhan-1 D614G spike mutant”.
  • Concerns associated with it are that the spike mutations could lead to antigenic changes that are detrimental to monoclonal antibody therapies and vaccine protection.
• Brazilan Variant
  • This is called P.1, a branch of the B.1.1.28 lineage.
  • Public Health England has designated this too as a variant of concern as it shares some mutations with the South Africa variant, such as E484K and N501Y.
• B.1.617 Double mutant
  • This variant is common in India and has a couple of defining mutations, E484Q and L425R, that enable them to become more infectious as well as evade antibodies
  • Though these mutations have individually been found in several other coronavirus variants, the presence of both these mutations together has been first found in some coronavirus genomes from India.
  • This is a homegrown variant and widely spread internationally.
  • It is worrying because the mutations E484Q and L452R are linked to increased infectivity.
  • L452R could even make the coronavirus resistant to T cells, which are a class of cells necessary to target and destroy virus-infected cells.

COVID-19 Vaccine:

• A COVID19 vaccine is a vaccine designed to provide acquired immunity against the virus that causes coronavirus disease 2019 (COVID19), severe acute respiratory syndrome coronavirus 2 (SARSCoV2).
• Prior to the COVID19 pandemic, there was a well-established body of knowledge about the structure and function of coronaviruses that cause diseases such as SARS and the Middle East respiratory syndrome (MERS), allowing for the rapid development of various vaccine technologies in early 2020.
• Many countries have implemented phased distribution plans that prioritize those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers.
• Equitable access to safe and effective vaccines is critical to ending the COVID-19 pandemic, so it is hugely encouraging to see so many vaccines proving and going into development. WHO is working tirelessly with partners to develop, manufacture and deploy safe and effective vaccines.
• India: On 16 January 2021 India started its national vaccination program against the SARS-CoV-2 virus which has caused the COVID-19 pandemic. The drive prioritizes healthcare workers and frontline workers, and then those over the age of 60, and then those over the age of 45 and suffering from certain comorbidities.

Conclusion

All the vaccines on offer in the United States or the United Kingdom have some insufficient, nonetheless efficacy data and therefore inspire greater confidence. Rather than dismiss concerns as ‘rumour mongering’ and ‘politically motivated’, the government has to work doubly hard to ensure that an honest appraisal of the vaccine’s prowess is rapidly disseminated. Those lining up for shots are adults – and a significant fraction of them far more medically literate than the average Indian – and all arms of government must treat them so. It is their experience that will percolate and influence the adoption of the vaccines among the larger population.