Vaccination is one of the great public health achievements of human history.

Vaccines used in national

immunization programmes (NIPs) are considered safe and effective when used correctly. Vaccines are,
however, not risk-free and adverse events will occasionally occur following vaccination. Public trust in
vaccine safety is key to the success of vaccination programmes.

Different Types of Vaccines

Preparation of measles vaccine

WHO via Images from the History of Medicine (NLM)
The first human vaccines against viruses were based using weaker or attenuated viruses to
generate immunity. The smallpox vaccine used cowpox, a poxvirus that was similar enough
to smallpox to protect against it but usually didn’t cause serious illness. Rabies was the first
virus attenuated in a lab to create a vaccine for humans.

Vaccines are made using several different processes. They may contain live viruses that
have been attenuated (weakened or altered so as not to cause illness); inactivated or killed
organisms or viruses; inactivated toxins (for bacterial diseases where toxins generated by
the bacteria, and not the bacteria themselves, cause illness); or merely segments of the
pathogen (this includes both subunit and conjugate vaccines).

Vaccine type Vaccines of this type on U.S. Recommended Childhood

6) Immunization Schedule

Live, attenuated Measles, mumps, rubella (MMR combined vaccine)

Varicella (chickenpox)
Influenza (nasal spray)
Rotavirus

Inactivated/Killed Polio (IPV)

Hepatitis A

Toxoid (inactivated toxin) Diphtheria, tetanus (part of DTaP combined immunization

Subunit/conjugate Hepatitis B
Influenza (injection)
Haemophilus influenza type b (Hib)
Pertussis (part of DTaP combined immunization)
Pneumococcal
Meningococcal

Vaccine type Other available vaccines

 Live, attenuated Zoster (shingles)
Yellow fever

Inactivated/Killed Rabies

Subunit/conjugate Human papillomavirus (HPV)

Live, attenuated vaccines currently recommended as part of the U.S. Childhood

Immunization Schedule include those against measles, mumps, and rubella (via the
combined MMR vaccine), varicella (chickenpox), and influenza (in the nasal spray version
of the seasonal flu vaccine). In addition to live, attenuated vaccines, the immunization
schedule includes vaccines of every other major type—see the table above for a breakdown
of the vaccine types on the recommended childhood schedule.

The different vaccine types each require different development techniques. Each section
below  addresses one of the vaccine types.

Live, Attenuated Vaccines

Attenuated vaccines can be made in several different ways. Some of the most common
methods involve passing the disease-causing virus through a series of cell cultures or
animal embryos (typically chick embryos). Using chick embryos as an example, the virus is
grown in different embryos in a series. With each passage, the virus becomes better at
replicating in chick cells, but loses its ability to replicate in human cells. A virus targeted for
use in a vaccine may be grown through—“passaged” through—upwards of 200 different
embryos or cell cultures. Eventually, the attenuated virus will be unable to replicate well (or
at all) in human cells, and can be used in a vaccine. All of the methods that involve passing
a virus through a non-human host produce a version of the virus that can still be recognized
by the human immune system, but cannot replicate well in a human host.
When the resulting vaccine virus is given to a human, it will be unable to replicate enough to
cause illness, but will still provoke an immune response that can protect against future
infection.

One concern that must be considered is the potential for the vaccine virus to revert to a
form capable of causing disease. Mutations that can occur when the vaccine virus
replicates in the body may result in more a virulent strain. This is very unlikely, as the
vaccine virus’s ability to replicate at all is limited; however, it is taken into consideration
when developing an attenuated vaccine. It is worth noting that mutations are somewhat
common with the oral polio vaccine (OPV), a live vaccine that is ingested instead of
injected. The vaccine virus can mutate into a virulent form and result in rare cases of
paralytic polio. For this reason, OPV is no longer used in the United States, and has been
replaced on the Recommended Childhood Immunization Schedule by the inactivated polio
vaccine (IPV).

Protection from a live, attenuated vaccine typically outlasts that provided by a killed or
inactivated vaccine.

Live-attenuated vaccines
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:

 Because they contain a small amount of the weakened live virus, some people
should talk to their health care provider before receiving them, such as people
with weakened immune systems, long-term health problems, or people who’ve
had an organ transplant.
 They need to be kept cool, so they don’t travel well. That means they can’t be
used in countries with limited access to refrigerators.
Live vaccines are used to protect against:
  Measles, mumps, rubella (MMR combined vaccine)
 Rotavirus
 Smallpox
 Chickenpox
 Yellow fever

Killed or Inactivated Vaccines

One alternative to attenuated vaccines is a killed or inactivated vaccine. Vaccines of this
type are created by inactivating a pathogen, typically using heat or chemicals such as
formaldehyde or formalin. This destroys the pathogen’s ability to replicate, but keeps it
“intact” so that the immune system can still recognize it. (“Inactivated” is generally used
rather than “killed” to refer to viral vaccines of this type, as viruses are generally not
considered to be alive.)

Because killed or inactivated pathogens can’t replicate at all, they can’t revert to a more
virulent form capable of causing disease (as discussed above with live, attenuated
vaccines). However, they tend to provide a shorter length of protection than live vaccines,
and are more likely to require boosters to create long-term immunity. Killed or inactivated
vaccines on the U.S. Recommended Childhood Immunization Schedule include the
inactivated polio vaccine and the seasonal influenza vaccine (in shot form).

Inactivated vaccines
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:

 Hepatitis A
 Flu (shot only)
  Polio (shot only)
 Rabies

Toxoids
Some bacterial diseases are not directly caused by a bacterium itself, but by a toxin
produced by the bacterium. One example is tetanus: its symptoms are not caused by
the Clostridium tetani bacterium, but by a neurotoxin it produces (tetanospasmin).
Immunizations for this type of pathogen can be made by inactivating the toxin that causes
disease symptoms. As with organisms or viruses used in killed or inactivated vaccines, this
can be done via treatment with a chemical such as formalin, or by using heat or other
methods.

Immunizations created using inactivated toxins are called toxoids. Toxoids can actually be
considered killed or inactivated vaccines, but are sometimes given their own category to
highlight the fact that they contain an inactivated toxin, and not an inactivated form of
bacteria.

Toxoid immunizations on the U.S. Recommended Childhood Immunization schedule

include the tetanus and diphtheria immunizations, which are available in a combined form.

Toxoid vaccines
Toxoid vaccines use a toxin (harmful product) made by the germ that causes a disease.
They create immunity to the parts of the germ that cause a disease instead of the germ
itself. That means the immune response is targeted to the toxin instead of the whole
germ.

Like some other types of vaccines, you may need booster shots to get ongoing
protection against diseases.

Toxoid vaccines are used to protect against:

 Diphtheria
 Tetanus
Subunit and Conjugate Vaccines
Both subunit and conjugate vaccines contain only pieces of the pathogens they protect
against.

Subunit vaccines use only part of a target pathogen to provoke a response from the
immune system. This may be done by isolating a specific protein from a pathogen and
presenting it as an antigen on its own. The acellular pertussis vaccine and influenza vaccine
(in shot form) are examples of subunit vaccines.

Another type of subunit vaccine can be created via genetic engineering. A gene coding for a
vaccine protein is inserted into another virus, or into producer cells in culture. When the
carrier virus reproduces, or when the producer cell metabolizes, the vaccine protein is also
created. The end result of this approach is a recombinant vaccine: the immune system will
recognize the expressed protein and provide future protection against the target virus. The
Hepatitis B vaccine currently used in the United States is a recombinant vaccine.

Another vaccine made using genetic engineering is the human papillomavirus (HPV)
vaccine. Two types of HPV vaccine are available—one provides protection against two
strains of HPV, the other four—but both are made in the same way: for each strain, a single
viral protein is isolated. When these proteins are expressed, virus-like particles (VLPs) are
created. These VLPs contain no genetic material from the viruses and can’t cause illness,
but prompt an immune response that provides future protection against HPV.

Conjugate vaccines are somewhat similar to recombinant vaccines: they’re made using a
combination of two different components. Conjugate vaccines, however, are made using
pieces from the coats of bacteria. These coats are chemically linked to a carrier protein, and
the combination is used as a vaccine. Conjugate vaccines are used to create a more
powerful, combined immune response: typically the “piece” of bacteria being presented
would not generate a strong immune response on its own, while the carrier protein would.
The piece of bacteria can’t cause illness, but combined with a carrier protein, it can
generate immunity against future infection. The vaccines currently in use for children
against pneumococcal bacterial infections are made using this technique.

Subunit, recombinant, polysaccharide, and

conjugate vaccines
Subunit, recombinant, polysaccharide, and conjugate vaccines use specific pieces of
the germ — like its protein, sugar, or capsid (a casing around the germ).

Because these vaccines use only specific pieces of the germ, they give a very strong
immune response that’s targeted to key parts of the germ. They can also be used on
almost everyone who needs them, including people with weakened immune systems
and long-term health problems.

One limitation of these vaccines is that you may need booster shots to get ongoing
protection against diseases.

These vaccines are used to protect against:

 Hib (Haemophilus influenzae type b) disease

 Hepatitis B
 HPV (Human papillomavirus)
 Whooping cough (part of the DTaP combined vaccine)
 Pneumococcal disease
 Meningococcal disease
 Shingles