DNA vaccination is a technique for protecting against disease by injection with genetically engineered plasmid containing the DNA sequence encoding the antigen(s) against which an immune response is sought, so cells directly produce the antigen, causing a protective immunological response DNA vaccines have potential advantages over conventional vaccines, including the ability to induce a wider range of immune response types. Several DNA vaccines are available for veterinary use. Currently no DNA vaccines have been approved for human use. Research is investigating the approach for viral, bacterial and parasitic diseases in humans, as well as for several cancers.
Vaccines based on messenger RNA (mRNA), an intermediary between DNA and protein, also are being developed. Recent technological advances have largely overcome issues with the instability of mRNA and the difficulty of delivering it into cells, and some mRNA vaccines have demonstrated encouraging early results. For example, NIAID-supported researchers developed an experimental mRNA vaccine that protected mice and monkeys against Zika virus infection after a single dose.
Inactivated vaccines use the killed version of the germ that causes a disease.
Inactivated vaccines usually don’t provide immunity (protection) that’s as strong as live vaccines. So you may need several doses over time (booster shots) in order to get ongoing immunity against diseases. Inactivated vaccines are used to protect against:
Live vaccines use a weakened (or attenuated) form of the germ that causes a disease.
Because these vaccines are so similar to the natural infection that they help prevent, they create a strong and long-lasting immune response. Just 1 or 2 doses of most live vaccines can give you a lifetime of protection against a germ and the disease it causes.
But live vaccines also have some limitations. For example:
One method of production involves isolation of a specific protein from a virus and administering this by itself. A weakness of this technique is that
isolated proteins can be denatured and will then become associated with antibodies different from the desired antibodies. A second method of making a
subunit vaccine involves putting an antigen's gene from the targeted virus or bacterium into another virus (virus vector), yeast (yeast vector), as in
the case of the hepatitis B vaccine or attenuated bacterium (bacterial vector) to make a recombinant virus or bacteria to serve as the important
component of a recombinant vaccine (called a recombinant subunit vaccine).
In structural biology, a protein subunit is a single protein molecule that assembles (or "coassembles") with other protein molecules to form a protein complex. Some naturally occurring proteins have a relatively small number of subunits and therefore described as oligomeric, for example hemoglobin or DNA polymerase.
Instead of the entire pathogen, subunit vaccines include only the components, or antigens, that best stimulate the immune system. Although this design can make vaccines safer and easier to produce, it often requires the incorporation of adjuvants to elicit a strong protective immune response because the antigens alone are not sufficient to induce adequate long-term immunity.
Including only the essential antigens in a vaccine can minimize side effects, as illustrated by the development of a new generation of pertussis (whooping cough) vaccines. The first pertussis vaccines, introduced in the 1940s, comprised inactivated Bordetella pertussis bacteria. Although effective, whole-cell pertussis vaccines frequently caused minor adverse reactions such as fever and swelling at the injection site. This caused many people to avoid the vaccine, and by the 1970s, decreasing vaccination rates had brought about an increase in new infections.
Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. Viruses have evolved specialized
molecular mechanisms to efficiently transport their genomes inside the cells they infect. Delivery of genes, or other genetic material,
by a vector is termed transduction and the infected cells are described as transduced. Molecular biologists first harnessed this machinery in the 1970s.
Paul Berg used a modified SV40 virus containing DNA from the bacteriophage λ to infect monkey kidney cells maintained in culture.
Viral vectors were originally developed as an alternative to transfection of naked DNA for molecular genetics experiments. Compared to traditional methods such as calcium phosphate precipitation, transduction can ensure that nearly 100% of cells are infected without severely affecting cell viability. Furthermore, some viruses integrate into the cell genome facilitating stable expression.
Protein coding genes can be expressed using viral vectors, commonly to study the function of the particular protein. Viral vectors, especially retroviruses, stably expressing marker genes such as GFP are widely used to permanently label cells to track them and their progeny, for example in xenotransplantation experiments, when cells infected in vitro are implanted into a host animal.
Gene insertion is cheaper to carry out than gene knockout. But as the silencing is sometimes non-specific and has off-target effects on other genes, it provides less reliable results. Animal host vectors also play an important role.
These vaccines use a well-established inactivated or killed viral vector such as adenovirus to express proteins of SARS-CoV-2 so that the proteins can be recognised by the immune system to elicit an immune response.
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material.
They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into
the virus-like structure.Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs.
VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera. VLPs have been produced from components of a wide variety of virus families including Parvoviridae (e.g. adeno-associated virus), Retroviridae (e.g. HIV), Flaviviridae (e.g. Hepatitis C virus), Paramyxoviridae (e.g. Nipah) and bacteriophages. VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells.