VACCINES!

There are two aspects to the prevention and treatment of virus diseases: prevetion where vaccination and public health measures. The other type being is treatment by antiviral drugs. Vaccine is a preparation of bacterial antigens that are induced into the immune system.

 Vaccine may contain killed, inactivated, dead or alive bacteria. Immunization is a result of good vaccination.  In the past and still today, immunisation programmes are held between herd immunity. This is when most of a population is immune against a certain infection, making it difficult for that specific bacteria/virus to find an individual who is not immune and thus cause infection and because they are not motile the can die out. Vaccines used in herd immunity have been created against smallpox & measles and many more are in progress.

Vaccine that have been given to those who are immune against certain viruses are known as ‘active’, but when women are given this virus and it is passed to the child via placenta this is known as ‘passive’. Hence the child would still require a MMR jab after the first birthday.

The types of vaccines produced can be broken down into four categories: the first is called killed/inactivated. The virus is treated with heat or chemicals so that it is no longer infectious. These vaccines stimulate good antibody responses, but because the virus is no longer infectious do not stimulate cell-mediated immunity. This type of vaccine was first used in 1885 by Louis Pasteur. A child was infected with rabies by a dog (bitten). Louis used this type of vaccine and induced to the child and it was successful. In 1950 another rabies vaccine was produced of this type, but failed as it needed was in an active form and multiplied. Other than reactivation, another disadvantage is that large scale production is required. In contrast to this vaccines drawbacks: it is cheap, simple and has low risk s of contamination. 

Another type of vaccine that can be produced is called attenuated virus. Attenuated pathogens are still viable and cause infection but do not cause disease. Attenuation is usually achieved by growing the organism in cells o other species so the pathogen becomes adapted to cells of other species and grows poorly in human cells. They can stimulate cell-mediated and antibody responses.  An example of this type of virus was introduced in 1977 by Edward Jenner. He used cow pox to induce into a child who was infected with small pox. Cox pox was similar but with less virulent factors. The immune system would have recognised this pathogen and eliminated small pox. This was a successful vaccine programme and is used in herd immunity. However it can show small signs of illness but it can also contaminate and virus shed. Amongst the advantages are: cheap, simple and long lasting.

In relation to subunit vaccines, many bacteria produce a polysaccharide coat that prevents phagocytosis in the absence of antibodies. Vaccination with the polysaccharide activates antibodies and is enough to provide immunity. Another type of vaccine that can be used is called purified subunits. This is usually done with influenza as it can produce new strains each year (antigenic drift). This type of vaccine is easier to store, low risk of contamination and targets immune response. Disadvantages= expensive, requires activation and complex. 

Finally we have cloned vaccine. This is when a virus or bacteria are cloned based on their surface antigen structure. They are usually cloned onto yeast cells which are then recognised by the immune system. It can be expensive, low cost can depends on infection, stable, no risk of contamination.

Why are current viral vaccines more effective than antiviral chemotherapy? what are the limitations of viral vaccines?

The control of viruses and viral diseases is accomplished in two different ways: vaccines help in the prevention of viral infections whilst antiviral drugs provide treatment of diseases induced by viruses. In animals (including humans), immunisation with vaccines has been far more effective than the use of antiviral drugs, Vaccines have however been very successful in preventing some viral diseases. Nevertheless, vaccines are difficult to successfully deploy against rapidly mutating viruses, such as Influenza virus and HIV and in individuals who are already infected with a virus, they provide modest or no therapeutic effect. That is why antiviral drugs, that are capable of preventing an infection or stopping it once started, are important as a second arm of antiviral defence.

A vaccine is valuable in controlling viruses and the diseases they cause, but it has to follow certain prerequisites to be effective. First of all, a vaccine must be safe: its side effects must be minimal and it should induce protective immunity in the population as a whole, evoking innate, cell-mediated and humoral responses. Not every individual in a population needs to be immunised to stop viral spread, but a sufficient number must become immune to prevent virus transmission. Protection provided by a vaccine should be long-term, meaning that more than one inoculation may be necessary in some cases. In practical terms, an effective vaccine should be biologically stable: there should be no genetic reversion to virulence and it should be able to survive storage and use in different conditions. Vaccines should also be easy to administer at low cost.

Viral vaccines can be classified broadly into two general groups: live attenuated virus vaccines and inactivated (killed) virus vaccines. In relation to live attenuated viral vaccines; the process of producing a virus strain that causes a reduced amount of disease. An attenuated virus is therefore a weakened, less virulent virus. A vaccine with low pathogenic potential that is, nevertheless, capable of inducing a long-lived, protective immune response. Live virus vaccines allow the activation of all components of the immune system yielding both a balanced systemic and local immune response, and a balanced humoral and cell mediated response. Also it stimulates an immune response to each of the antigens of a virus. As demonstrated in a study on Influenza A virus vaccines, immunity induced by live virus vaccines is generally more durable and more effective than that induced by inactivated virus vaccines.

Examples of effective killed virus vaccines administered to humans are the inactivated HPV, Influenza virus, Hepatitis A virus and Rabies virus vaccines. The basis for the construction of an inactivated vaccine is the isolation of virions of the virus of interest and their subsequent inactivation by chemical or physical procedures. The infectivity of the virus is eliminated, but the viral antigenicity should not be compromised by these treatments. Common techniques include treatment with formalin (chemical) or disruption with a detergent (e.g. for influenza). The level of efficacy of these vaccines differs: inactivated PV is highly effective in preventing disease, whereas the Influenza virus vaccine is only partially protective.

Antiviral drugs are a class of medication used specifically for treating viral infections. The emergence of antiviral drugs is expanding knowledge of the genetic and molecular function of viruses, major advances in the techniques for finding new drugs, and the intense pressure to deal with HIV. The general idea behind antiviral drug design is to identify target viral proteins, or parts of proteins, that can be disabled. These targets should be common across many strains of a virus, or even among different species of viruses in the same family, so a single drug will have a broad effectiveness. Once targets are identified, candidate drugs can be selected. High throughput screening (HTS) allows a researcher to effectively conduct millions of biochemical, genetic or pharmacological tests in a short period of time. Through this process one can rapidly identify active compounds, antibodies or genes which modulate a particular biomolecular pathway. The results of these experiments provide starting points for drug design and for understanding the interaction or role of a particular biochemical process in biology.

There are two main difficulties with antiviral drugs. First there is the problem that by the time clinical signs and symptoms appear in acute infections, virus replication has reached such a peak that the antiviral has little therapeutic effect. The other problem is that virus multiplication is tied so intimately to certain cellular processes that most antivirals cannot discriminate between them. However, viruses do have unique features, so specific antivirals should be able to serve as effective chemotherapeutic agents. An antiviral would be effective if it inhibited any stage of virus multiplication: attachment, replication, transcription, assembly or release of progeny virus particles. The current major antivirals act in one of these ways. Most of the antivirals now available are designed to help deal with HIV; Herpesvirus, which is best known for causing cold sores but actually covers a wide range of diseases; and HBV and HCV, which can cause liver cancer.

A well designed and implemented vaccination program is a key element, however, it is important to understand and appreciate the limitations. No vaccination program can fully prevent disease. Vaccines do not prevent infection rather they prime the immune system to provide a rapid and effective response following infection. This limits multiplication and spread of the infectious agent and lessens tissue damage. The result is decreased disease severity and decreased transmission to other people.

There are some cases in which an inactivated virus vaccine has amplified disease rather than prevented it. This was first observed with a formalin-inactivated MeV vaccine. This vaccine prevented measles initially, but after several years, vaccines lost their resistance to infection and when subsequently infected with naturally circulating MeV, patients developed an atypical illness with accentuated symptoms. A further disadvantage is that inactivated virus vaccines often do not induce CTL cells as efficiently as live attenuated viral vaccines. Furthermore, to induce the same immune response as live attenuated preparations, inactivated virions require mixing with adjuvants, which are substances that stimulate early processes in immune recognition, particularly the inflammatory response. Adjuvants can mimic or induce cellular damage, stress and release of heat shock proteins which directly stimulate the immune system. Another major disadvantage is that, as the killed virus cannot multiply, the immunising dose has to contain far more virus that a dose of live vaccine and repeated doses may be required to induce adequate levels of immunity; this increases the overall cost of the vaccine.

There are also some major concerns regarding live virus vaccines. Firstly, they can contain foreign agents (contamination), although this has rarely been a problem. They can cause illness directly or lose their attenuation during manufacture or during replication in vaccines by reversion or second-site compensatory mutations. Given the high rate of mutation associated with RNA virus replication, a reversion to virulence may occur quite frequently. Some live virus vaccines, such as the MeV, Rubella virus and Yellow Fever virus vaccines, retain a low level of residual virulence. Others, such as the PV vaccine, may restore a varying degree of virulence during infection by the vaccine virus, although this occurs at an extremely low frequency. Another disadvantage is that live viral vaccines can lose infectivity during storage, transport or use. Also, naturally occurring wild-type viruses may interfere with infection by a live virus vaccine, resulting in a decrease in vaccine efficacy. Stability is also a serious problem with labile vaccine viruses such as MeV. The measles vaccine needs to be stored and transported at low temperature (4°C).