University of South Florida Medical Microbiology COVID-19 Vaccines Discussion

Discuss the different methodologies of producing vaccines. Select, justify and outline the steps of one methodology that you would use to produce an effective, safe vaccine against COVID-19, starting from identifying the viral epitope or component as an immunogen to production of an effective and safe vaccine.

VACCINES
 Generate immunity to an infection or disease
 Prevent and/or decreases serious symptoms of diseases as
pertussis, diphtheria, tetanus, rabies
 Help in protection and control disease transmission of
diseases as measles,mumps, rubella, influenza, rotavirus,
Hib
 are the basis of immunization which generates faster and
stronger immune responses in immunized individuals than
in nonimmunized
 Vaccines (immunization) + vector eradication + quarantine
(limiting exposure of healthy to infected people) can prevent
or eliminate diseases (polio, smallpox, measles) and create
herd immunity
Table 17.3
Vaccine-Preventable Diseases
 Bacteria
 Viral
 Pertussis
 Measles
 Mumps
 Rubella
 Diphtheria
 Hemophilus pneumonia
/meningitis
 Pneumococcus pneumo
and meningitis
 Meningococcal meningitis
 Tetanus
 Influenza
 Rotavirus
 Rabies
 Polio
Vaccine preventable diseases occur due
to:
 Unavailability of immunization programs
 Immunization is very expensive as in developing
countries
 Misinformation
 Cultural and/or religious beliefs (polio in Pakistan,
measles in USA)
Properties of an Ideal Vaccine
 Microbe causes significant illness
 Microbe exists as only one serotype
 Vaccine is heat stable, safe and protective
 Cost of vaccine is affordable
 Induces humoral and/or cellular immune responses that
block infection or systemic spread
 Vaccine does not cause adverse reactions
 Vaccine protects recipient and population at risk
Types of Vaccines/Immunizations
Types of Immunization
 Passive and Active
 Passive (immunity generated from)
 Injection of purified antibody, aby-containing, immune cells for
temporary protection from a known exposure (HBIg, VZIg, Tig,
Rig) hepatitis, variella, tetanus, rabies.
 Neonates receiving maternal abys via placenta and from
maternal milk
 Therapeutic abys that prevent cellular responses in
autoimmune diseases
 Protect immunodeficient patients
 Block cytokine storms
Passive Immunization
The injection of purified antibody or antibody-containing serum to provide
rapid, temporary protection or treatment of a person
Newborns receive natural passive immunity from maternal immunoglobulin
that crosses the placenta or is present in the mother’s milk.
 To prevent disease after a known exposure (e.g., needlestick injury with
blood that is contaminated with hepatitis B virus)
 To ameliorate the symptoms of an ongoing disease
 To protect immunodeficient individuals
 To block the action of bacterial toxins and prevent the diseases they
cause (i.e., as therapy)
Immune Globulins Available for
Postexposure Prophylaxis
Disease
Source
Hepatitis A
Human
Hepatitis B
Human
Measles
Human
Rabies
Human †
Chickenpox, varicella-zoster
Cytomegalovirus
Human†
Human
Tetanus
Human, † equine
Botulism
Equine
Diphtheria
Equine
Types of Immunization
 Passive and Active
 Active (immunity generated from)
1. a challenge infection or immunogen (natural immunization)
2. vaccination: immunity generated from exposure to microbes or
antigens against secondary challenge
 Live vaccines (vaccinia, polio)
 Inactivated, subunit, killed vaccines
 DNA vaccines: plasmid DNA injected into muscle or skin and
taken up by dendritic cells or macrophages which then express
the gene for the immunogen
Types of immunizations
. Antibodies (passive immunization) can be provided to block the
action of an infectious agent, or an immune response can be
elicited (active immunization) by natural infection or vaccination.
The different forms of passive and active immunization are
indicated. A, Equine antibodies can be used if human antibody is
not available. B, Vaccine can consist of components purified from
the infectious agent or can be developed through genetic
engineering (VLP [virus-like protein]). C, Vaccine selected by
passage in animals, embryonated eggs, or tissue culture cells. D,
Deletion, insertion, reassortment, and other laboratory-derived
mutants. E, Vaccine composed of a virus from a different species,
which has a common antigen with the human virus.
Active Immunization
 occurs when an immune response is stimulated because of
challenge with an immunogen, such as exposure to an
infectious agent (natural immunization) or through
exposure to microbes or their antigens in vaccines. On
subsequent challenge with the virulent agent, a secondary
immune response is activated that is faster and more
effective at protecting the individual, or antibody is present
to block the spread or function of the agent.
Bacterial Vaccines
Bacteria (Disease)
Vaccine Components
*
Who Should ReceiveVaccination
Corynebacterium diphtheriae
(diphtheria)
Clostridium tetani (tetanus)
Toxoid
Toxoid
Bordetella pertussis (pertussis)
Killed cell or acellular
Haemophilus influenzae B (Hib)
Capsule polysaccharide;
Children and adults
Children and adults
Children
capsule polysaccharide-protein conjugate
Children
Neisseria meningitidis A and C
(meningococcal disease)
Capsule polysaccharide
People at high risk (e.g., those
with asplenia), travelers to epidemic areas
(e.g., military personnel), children
Streptococcus pneumoniae
(pneumococcal disease; meningitis)
Capsule polysaccharides;
capsule polysaccharide-protein conjugate
People at high risk (e.g., those with
asplenia), children, the elderly
Capsular polysaccharide conjugate vaccines
Capsular polysaccharide conjugate vaccines. Capsular polysaccharides are poor
immunogens, do not elicit T-cell help, and only elicit IgM without memory. Capsule
polysaccharide conjugated to a protein (e.g., diphtheria toxoid) binds to surface
antipolysaccharide IgM on the B cell, the complex is internalized, processed and then a
peptide is presented on MHC II to CD4 T cells. The T cells become activated, produce
cytokines, and promote immunoglobulin class switching for the polysaccharide specific
B cell. The B cell can become activated, make IgG, and memory cells will develop
Types of Viral Vaccines
 Live Vaccine
 Killed Vaccine
 Attenuated Vaccine
 DNA Vaccine
Live viral vaccines are prepared using attenuated strains of
otherwise pathogenic viruses. The attenuation process is
highly variable, ranging from sequential passaging of a virulent
viral strain in cell cultures in an effort to select progeny virions
that have lost the capacity to cause disease but retain potent
immunogenicity to the incorporation of temperature-sensitive
mutant strains. The FluMist nasal influenza virus vaccine
contains cold-adapted strains of Type A and Type B influenza
viruses. These vaccine strains grow optimally at 25˚C and
poorly at 37 ˚C.
Killed virus vaccines are prepared from viral stocks that have
been inactivated with Beta-propiolactone or formaldehyde
under controlled conditions of pH, osmolarity and a high level
of purification of the viral suspension.
As shown in the next table, there are fifteen (15) viral
vaccines that are currently licensed by the FDA for use in the
United States.
Advantages and Disadvantages of Live versus Inactivated
Vaccines
Property
Route of administration
Live
Natural* or injection
Inactivated
Injection
Dose of virus, cost
Low
Number of doses
Single †
Multiple
Need for adjuvant
No
Yes ‡
Duration of immunity
High
Long-term
Short-term
Antibody response
IgG, IgA§
IgG
Cell-mediated immune response
Good
Heat lability in tropics
Interference¶
Side effects
Reversion to virulence
Poor
Yes |
No
Occasional
None
Occasional mild symptoms #
Rarely
Occasional sore arm
None
*Oral or respiratory, in certain cases.
†A single booster may be required (yellow fever, measles, rubella) after 6 to 10 years.
‡However, the commonly used alum is inefficient.
§IgA if delivered via the oral or respiratory route. Oral polio vaccine can prevent wild-type poliovirus from multiplying in the gut.
|Magnesium chloride and other stabilizers and cold storage assist preservation.
¶Interference from other viruses or diseases.
#Especially rubella and measles
Although vaccination to prevent viral diseases is clearly in the forefront of intervention
strategy, this approach is not perfect. As shown in the table below, there are problems
associated with the use of either “live” or “killed” viral vaccines .
Characteristics of Live and Killed Viral Vaccines
Characteristic
Live Vaccine
Killed Vaccine
Duration of Immunity
Longer
Shorter
Effective of protection
Greater
Lower
Immunoglobulins
IgA1 and IgG
IgG
Yes
Weakly or none
More effective
Less effective
Reversion to virulence
Possible
No
Stability at room
Low
High
produced
Cell-mediated immunity
produced
Interruption of transmission
of virulent virus
temperature
Viral Vaccines
Virus Vaccine
Components
Polio Inactivated
Who Should Receive Vaccinations
(inactivated polio vaccine, Salk vaccine)
Children
Attenuated (oral polio vaccine, Sabin vaccine)
Children
Measles
Attenuated
Children
Mumps
Attenuated
Children
Rubella
Attenuated
Children
Varicella-zoster
Attenuated
Children
Rotavirus
Human-bovine hybrids
Human papilloma virus (HPV) Virus-like particle (VLP)
Influenza
Inactivated
Infants
Girls aged 9-26
Adults, especially medical personnel
and the elderly
Attenuated (nasal spray)
Hepatitis B
5-50 yr
Subunit (VLP)
Newborns, health care workers, high-risk groups
(e.g., sexually promiscuous, intravenous drug
users)
Current Viral Vaccines 2018
Usage
Common
Special situations
Vaccine
Live Virus, Killed Virus, or Subunit of Virus
Measles
Mumps
Rubella
Varicella (chickenpox)1
Polio
Influenza
Hepatitis A
Hepatitis B
Rabies
Rotavirus5
Human papilloma virus
Yellow fever6
Japanese encephalitis6
Adenovirus
Smallpox7
Live
Live
Live
Live
Live and Killed2
Live and killed (purified subunits)3
Killed
Subunit4
Killed
Live
Live
Live
Killed
Live
Live
Vaccines for 0-6 year olds
As shown in the next table, there is a subset of viral and bacterial vaccines that are
recommended for children aged 0 – 6 years.
Vaccines Recommended for Children Aged 0 – 6 Years (2012)1,2
Viral Vaccines3
Bacterial Vaccines
Diptheria toxoid, tetanus toxoid,
acellular pertussis (DTaP)
Haemophilus influenza type b (Hib)
Meningococcal
Pneumococcal
1
Hepatitis A
Hepatitis B
Influenza
Measles, mumps, rubella (MMR)
Poliovirus, inactivated
Rotavirus
Varicella
Vaccines are listed in alphabetical order.
A complete description of the vaccine schedule is available on the Centers for Disease Control
website, www.cdc.gov.
3 Human papilloma virus vaccine is recommended for females aged 9 to 26 years.
2
Vaccination coverage for target groups by vaccine, age