Vaccines

Question 1

What is vaccination?

Answer 1

Deliberate act of inducing adaptive immunity by injecting someone with a vaccine (dead, attenuated, non pathogenic) form of the pathogen.

Question 2

What are the two forms of passive immunity?

Answer 2

Natural - IgG transfer from mother to foetus, IgA in colostrum breast milk (few days after birth)

Active - Use of Abs (Roden/human/chimeric/humanized)

Question 3

How was passive immunity used against Ebola?

Answer 3

Ebola is a ssRNA filovirus which mainly infects endothelial cells, mononuclear phagocytes and hepatocytes - cause haemorrhage - NO VACCINE

Zmapp - 3 chimeric mAbs against glycoprotein produced by EBOV - produced by taking genes from hybridoma and replacing constant region with human genes. Then transfect into tobacco plant to express (pharming).

Tested in rhesus macaque - all survived

Used in 2014 ebola outbreak in W Africa - 7 given - 2 died - NS

Question 4

Discuss passive immunity against enterovirus?

Answer 4

Respiratory RNA virus - causes pneumonia in children/young adults
A6-1 targets VP-1 - shown to have benefits in mice

Question 5

What other disease can we use passive immunity techniques against?

Answer 5

Botulism - infant botulism - Baby BIG - IgG pooled from adults plasma immunised with pentavalent botulism toxin - select for high affinity against type A+B

Question 6

What cells are responsible for immunological memory?

Answer 6

Memory B and Memory T cells

Question 7

What are the advantages of memory B cells over naive t cells?

Answer 7

Higher frequency
Longer lasting
Higher IgG IgA amounts (effector Abs)
Increased somatic hypermutation

Question 8

What are the three types of T cell?

Answer 8

Naive - not yet seen antigen (CD45RA)
Effector - directs affects against antigen (Th1, Th2)
Memory - stays in blood to deal with future responses (CD45RO - associates with TCR and CD4)

Question 9

What are the two types of effector T cells?

Answer 9

Central Memory T cells - CD45RO, CCR7, CD62L, stays in lymph node - slower maturation to effector cells

Effector Memory T cells - CD45RO - loses CCR7 upon Ag stimulation - moves into tissues and releases cytokines etc.

Question 10

What are the main requirements for a vaccine?

Answer 10

Safe
Effective
Long lasting
Right response (B/T, Systemic/local)
Low cost
Stable
Easy to administer

Question 11

What are the different types of vaccine?

Answer 11

Live attenuated (Whole agent)
Killed (whole agent)
Recombinant subunit
Purified subunit
Conjugate

Question 12

Give examples of live attenuated? :)/:(

Answer 12

MMR, Oral polio (Sabin), BCG
:) - induce systemic and local response, can give via natural pathway, do not need booster shots
:( - can alter virulence, can become inactivated and may cause damage in immunocompromised host

Question 13

Give examples of killed? :)/:(

Answer 13

Salk Polio, pertussis, typhoid, cholera
Kill using formaldehyde - must ensure antigens do not get denatured
Wont induce disease, stable

Question 14

Give examples of recombinant subunit? :)/:(

Answer 14

HepB - HepBsAg

Avoids problems with bulk pathogen storage

Question 15

Purified subunit? :)/:(

Answer 15

HiB - purified capsular polysaccharides - meningitis

Influenza - purified H and N

Question 16

Conjugate? :)/:(

Answer 16

Fusion of polysaccharide - weak antigen + strong antigen - HiB conjugate vaccine (conjugated to tetanus, diptheria)

Question 17

What is an adjuvent?

Answer 17

Given with a vaccine to boost the immune response. Induces damage to host tissue

Question 18

Give 2 examples of adjuvent

Answer 18

Alum - PRR Nalp3 - Hib/pertussis/diptheria

MPLA - TLR4 - HiB