Immunology and vaccines

Question 1

What is the cut off for rabies antibody testing to be considered adequately immune?
Who should have this done?

Answer 1

minimum acceptable rabies antibody is 0.5 IU/mL

-immunosupressed: At day 30 of post-exposure (HRIG+ 5 doses at Day 0, 3, 7, 14, 30 if green or amber)
-those at high risk of exposure (lab staff, vets)

Question 1

List options for Dengue vaccination and pros and cons of each

Answer 1

Dengvaxia
Qdenga
Butantan

All “active” against all four serotypes
All are live attenuated

And can not be used in immunosupressed, pregnancy and breast feeding

Dengvaxia- need to check serostatus before giving it, otherwise risk of developing dengue infection

In the NEJM butantan trial: Only showed repsonse to DENV-1 and DEV-2 (just becuse there weren’t enough infections with 3 and 4 during the trial)

JCVI march statement: only recommends Q denga in those who have had dengue in the past

Question 2

What are methods of assessing vaccine efficacy?

Answer 2

• looking at disease outcome (ie did they develop the disease following vaccine
• Assessment for neutralising antibodies
  ( P/FRNT or VRNT) VRNT is higher through put (see below)
• Assessing T cell repsonse (more difficlut to do as requires PMBC). Includes Elispot, intracellular cytokine staining, T cell proliferation assays, ELISA to look for T -cell specific cytokines, T cell tetramer staining

The present gold standard for detecting neutralizing antibodies against many viruses, including dengue, is the plaque/focus reduction neutralization test (P/FRNT). The FRNT is a cell-based assay that inherits high variability, resulting in poor precision and has lengthy turnaround times. The virus reduction neutralization test (VRNT) is a high-throughput alternative to the standard low-throughput and laborious FRNT. The VRNT is similar to FRNT using unaltered wild-type virus and immunostaining, yet uses imaging cytometry to count virus-infected cells 1 day post-infection, reducing assay time and increasing overall throughput 15-fold. In addition, the VRNT has lowered variability relative to FRNT, which may be explained in part by the observation that foci overlap alters foci count and titer over time, in the FRNT. The ability to count one infected cell, rather than waiting for overlapping foci to form, ensures accuracy and contributes to the precision (7–25% coefficient of variation) and sensitivity of the VRNT.

https://www.nexcelom.com/applications/virology/antibody-neutralization/

Question 3

What is the name of the JE vaccine and what is the schedule

Answer 3

ixiaro (inactivated)
2 doses (0 and 28 days), can give extra dose afer 12 months for boosting

Question 4

What are some strategies for reducing myocarditis risk following COVID vaccination

Answer 4

1) Increasing duration between first and second dose
2) Choosing age appropriate strategies: eg highest risk is in those under 25, Pfizer BioNTech vaccine is the preferred vaccine for children due to a slightly lower reported
rate of myocarditis

Question 5

Contra-indication for Mpx Vaccination

Answer 5

Trick question- arent’ really any
- Anaphylaxis to chicken protein, gentamicin or cipro

Allergic dermatitis
- risk of skin reactions, need risk assessment prior

Not licensed in kids but has been used and its been fine, same for pregnanct women and breast feeding

Don’t use the intradermal on kids

Manufacteringprocess of imvabex: third gen smallpox vaccines,
modified vaccinia Ankara (MVA-BN) vaccine, a third generation smallpox vaccine
contains a replication defective virus. The virus used in the vaccine is attenuated through
multiple passages in chicken embryo fibroblast cells, leading to a substantial loss of its
genome including immune evasion and virulence factors. It demonstrates very limited
replication capability and low neuropathogenicity in human and animal studies, while
retaining immunogenic properties, including demonstrable protective immune responses
against a variety of orthopoxviruses (Verheust C et al, 2002). As MVA-BN cannot replicate
in mammalian cells it does not produce a lesion at the site of vaccination.

Question 6

What are the CI for intradermal administration of mpox vaccine (Vs IM or sub cutaneous)

Answer 6

Children
Immunosupressed
Keloid scarring

[ie only should be used in Individuals (18 years and above)
who are immunocompetent]

Question 7

Vaccines used in post exposure prophylaxis

Answer 7

HAV
Mpox
(MMR and VZV- if given with 72 hours)- in brackets as not in specific guidelines but notes it may be of benefit
Rabies

Question 8

What tests would you do on a HSCT recipient before transplant

Answer 8

BBV screen
-HIV, Hep B surface and core, HCV IgG (+/- RNA)
- including risk assessment (ie may need to to HCV RNA if high risk)
-Syphilis serology

CMV:
Donors or recipients who are initially found to be CMV IgG-negative should be retested pre-transplant to exclude primary CMV infection

All potential HSCT recipients should have CMV IgG tested at least twice prior to transplantation, separated in time as much as possible, to help identify any false-positive results

VZV
HEV

(?HSV, ?EBV)

Travel related
- Strongyloides

Question 9

What is the TBE vaccine schedule

Answer 9

T B E = 3 doses
0, 3 months and 15 months (12 months after second dose)

Neudorf strain vaccine

Question 10

How long should you wait to give flu vaccine if any influenza antivirals have been given

Answer 10

Applies to LAIV only
LAIV should be delayed until 48 hours following the cessation of treatment with influenza antiviral agents. Administration of influenza antiviral agents within 2 weeks of administration
of LAIV may adversely affect the effectiveness of the vaccine.

sideline Influenza “The person has been exposed to a person (in the same household or residential setting) with an influenza-like illness.”

Question 11

What is the window peroid for offering MVA-BN for PEP

Answer 11

within 4 days, but can give in up to 14 (if immunosupressed or continued expsoure)
Schedule is two doses 28 days apart

Question 12

Component of shingrix

Answer 12

The glycoprotein E is a protein present in the Varicella Zoster Virus.
The adjuvant (AS01B)

Recombinant vaccine

Question 13

component of CMV Vaccine

Answer 13

Moderna mrna 1647
Comprises six mRNAs encoding the
CMV pentamer complex and gB
antigens together into one vaccine

CMVictory trial

Question 14

What percentage of the population is protected from measles after 1 dose of MMR?

Answer 14

90%

Question 15

From what year do you presume there is little natural exposure to measles

Answer 15

1990

Question 16

What percentage of indivuals born before 1970 are antibody negative to measles

Answer 16

<1%

Question 17

Describe Group B ii from measles guideline

Answer 17

HSCT within 12 months
persistent agammglobulinaemia (IgG less than 3g/L
SCID

Give HNIG

Question 18

A single dose of MMR confers what percentage of protection against mumps

Answer 18

60-90%

Question 19

Infectious period of mumps

Answer 19

2 days before to 5 days after onset of symptoms

Question 20

Complications of MMR vaccination

Answer 20

ITP- if this occurs after first dose, then send bloods to check whether there is adequate protection. Usually occurs within 6 weeks on first dose

Question 21

Changes to routine vaccination schedule in UK

Answer 21

Bring forward 2nd dose of MMR to 18 months
Recommend bringing in VZV
Stop Men C, extra dose of Hib at 18 months

Question 22

Definition of heard immunity

Answer 22

Indirect protection from an infectious disease that happens when a population is immune either through vaccination or immunity developed through previous infection

Question 23

T/F you can give yellow fever and MMR together?

Answer 23

False
Attenuates MMR response

Question 24

Indications of Gardisal and schedule

Answer 24

A upto and including 45 years in MSM (2 dose schedule at 0 and 6-24, 3 dose schedule for immunosupressed)

1 dose schedule for those less than 25 (i.e) routine vaccination schedule

Question 25

Difference between fendrix and energix

Answer 25

Energix is yeast recombinant vaccine, needs to be given at double dose, ie. 2 X 20(for patients on dialysis and HIV)

Fendrix is has a double adjunct vaccine of monophosphorol lipid A- dose is 20

Question 26

Man gets bitten on leg by a dog in Ukraine (breaks through skin). He is immunocompetent, had one dose of Rabies vaccine prior to travel. Subsequent management

Answer 26

RED (Ukraine high risk country + dof bite breaking skin is Cat 3) Composite risk
4 doses of vaccine (0,3,7,21) +HRIG

Question 27

Re rabies: Describe category 2 exposure for
a) terrestrial animals
b) bats

Answer 27

a) Minimal contact with saliva
(as opposed to group 3 which is direct contact with saliva - as in, proper bite)
e.g bruises or abrasions, licks to insect bites, bites that do not break the skin

b) Uncertain physical contact

i.e. direct handling without gloves
* a bat tangled in hair
* potential contact with a bat in the UK or
Ireland in someone who is unable to give
an accurate history of an exposure (that
is, intoxicated individual, young child,
individual with mental impairment)
* any bat found in the room of a sleeping
person outside of the UK or Ireland

(that is,
where there has been no observed
direct physical contact (with saliva) but
this could have occurred)

Question 28

What is the recommended period for post exposure treatment of rabies when there is a bite to the head/neck

Answer 28

ASAP but within 12 hours

Note that if there has been an exposure to an animal that is suspected of having rabies in UK (as an example if a no risk country), typically you just observe the animal. However, if bite to head or neck, start PET

Question 29

Indications for 5 doses of rabies Vaccine, what is the schedule

Anything else you would do

Answer 29

Immunosupressed with red or amber composite risk
Schedule 0, 3, 7, 14, 30
Give alongside HRIG
Send sample for antibody testing on day 30

Question 30

Inidications for HRIG

STRUGGLING WITH THESE GUIDELINES- terrible question sorry

Answer 30

Immunosupressed (irrelevant of vaccine history)with red or amber composite risk

Partially vaccinated or non-vaccinated people with red composite exposure

Note fully immunised to not get HRIG- 2 doses of rabies vaccine if amber or red risk (full dose is three vaccines)

Question 31

When do you NOT give HRIG

Answer 31

fully vaccinated immunocompetent people
No risk countries
No exposure (ie no physical exposure to saliva of animal)

Question 32

Ixiaro: 1) what does it contain, what is the schedule

2) Indications

Answer 32

1) JE- inactivated vaccine, vero cells + adjuvunct

Note 50% of worlds JE is in China

1) Staying in JE are more than ONE month, frequent visits, living in area. Lab workers with J@

If none of above need to have other at risk things on itinerary- if staying less than a month + pig farm or rice fields

Consider if uncertainty of travel plans

Question 33

Indications for COVID vaccine in current season

Answer 33

Age over 75
In elderly care facility
Immunosupressed in those aged over 6 months

Monovalent mRNA vaccines targeting XBB strains are the only vaccines expected to be
deployed in the Spring 2024 programme

The following vaccines are advised for use in all individuals aged 18 years and over:

• Pfizer-BioNTech mRNA (Comirnaty) Omicron XBB.1.5 vaccine.
• Moderna mRNA (Spikevax) XBB.1.5 vaccine.

The following vaccines are advised for young people aged 6months to 17 years:

• Pfizer-BioNTech mRNA (Comirnaty) Omicron XBB.1.5 vaccine.

Novavax Matrix-M adjuvanted COVID-19 vaccine (Nuvaxovid - latest authorised and available vaccine) may be used as a booster dose for persons aged 12 years and above when alternative products are considered not clinically suitable.

HIPRA bivalent COVID-19 vaccine (Bimervax) may be used as a booster dose for persons aged 16 years and above (reference 3) when alternative products are considered not clinically suitable - see the COVID-19 chapter of the Green Book.

note: In the early summer of 2023, based on emerging evidence of superior immunogenicity
against matched strains with good evidence of back-boosting against historic strains,
regulators expressed a preference for moving from bivalent to monovalent variant vaccines.
Monovalent XBB mRNA vaccines produced by Pfizer and Moderna were approved by the
MHRA and first used in the Autumn 2023 programme.

Question 34

Components of Zostavax

Answer 34

Live, attenuated virus derived from the Oka/Merck strain of varicella
zoster virus, but at a significantly higher dose than the Varivax® varicella vaccine

From September 2023, Shingrix replaced Zostavax in the routine immunisation programme.
Shingrix® is a recombinant vaccine and contains varicella zoster virus glycoprotein E antigen
produced by recombinant DNA technology, adjuvanted with AS01B.

Question 35

Schedule of shingrix

Answer 35

2 doses 8 weeks apart
from age 60

Recombinant vaccine of the glycogoprotein E antigen (recombinant DNA technology + adjuvant)

Question 36

Vaccines which use recombinant DNA

Answer 36

HBV
(energix, fendrix
- note Fendrix®, for patients with renal insufficiency, is adjuvanted
by monophosophoryl lipid A, different form of adjuvunct)

Shingrix- of glycoprotein E

?HPV

Virus-like particles
(VLPs) are prepared from recombinant proteins grown in either yeast or baculovirus
infected insect cells (the latter derive from a type of moth). (Is this the same as recombinant DNA)

Influenza- QIVr: Contains ??? (INCOMPLETE)

Question 37

T/F can give LAIV 1 day after treatment with tamiflu?

Answer 37

F- should delay by 48 hours

There is a potential for influenza antiviral agents to lower the effectiveness of LAIV.
Therefore, influenza antiviral agents and LAIV should not be administered concomitantly.
LAIV should be delayed until 48 hours following the cessation of treatment with influenza
antiviral agents.
Administration of influenza antiviral agents within 2 weeks of administration of LAIV may
adversely affect the effectiveness of the vaccine.

Question 38

Influenza vaccine
Current types of available

Which are recommeneded

INCOMPLETE

Answer 38

NOTE all contain: h1n1 (pdm 2009), H3N2, B/austria, B/puket

1) LAIV
2) QIVc- for 18-65 (or QIVr)

3) QIVr (recombinant) - for over 65s and for at risk 18-65

4) aQIV - for over 65s (or QIVr)

1-2 for younger people
3-4 for over 65s

Note that in children in at risk groups

if age 6 months- 2 year give QIVc, if 2-18 offer LAIV as first line (QIVc as second line)

Should start from october

Question 39

HBV vaccine options (needs editing)

Answer 39

Recombinant DNA: Energix,fendrix (made by GSK), HBVaxPro (made by someone else but same thing
Heplisav-B which contains cytosine phosphoguanine (CpG) 1018 adjuvant and is administered as a 2-dose series at months 0 and 1.

Bivalent with HAV- Twinrix

tri-antigenic monovalent
vaccine comprising: PreHevbri®, which is a

3 dose: Engerix-B, Recombivax HB
* 2 dose: Heplisav-B- 2 doses over 1 month
* Higher vaccine completion rates
* Higher seroprotection rates than 3 dose: 90-95% vs 75-81%
* Response in people w HIV: 80-93%1-6
* Hemodialysis patients: 4 dose 89%7
* NEW- 3-antigen - PreHevbrio
* 3 hepatitis B surface antigens of the hepatitis B virus – S, pre-S1, and pre-S2
* Seroprotective rate 91.4-99% 8-9
* Immunogenicity develops sooner (high rate after 2nd dose)

Question 40

Vaccine Manufacturing process Comarnity (Pfizer-BioNTech)

Answer 40

covid- mRNA
XBB 1.5
Spike protein
Can be used from 6 months of age

Question 41

Vaccine Manufacturing process PreHevbri

Answer 41

Tri antigenic monovalent vaccine
S, pre-S1, pre-S2

Standard shecule 0,1,2,6

Question 42

Healthcare worker- 2 months post vaccine shedule anti-Hbs ab is 30. What do you do?

Answer 42

1) check which schedule they had- if it is the rapid course (0, 1, 2, 12) the bloods should have been done after the fourth dose
2) If taken at the correct time, give one booster then don’t check levels again

Rationale:
Some anti- Hbs are not good at lower limit

Note- immunity lasts 20-30 years, do not need reinforcing doses
Including for those that have had childhood vaccines

Question 43

Ebola vaccine options + manufacturing

INCOMPLETE

Answer 43

Ervebo aka ZEBOV- Live vaccine. Zaire only, vesicular stomatitis virus based with - one dose only

(NB this is different to what is given in healthcare workers- Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo)

RING vaccinations:
Aim is to vaccinate those close to inde case
Uses less total doses of vaccines
Involves seeking out those with potentil exposure
Resource intensive, as requires ongoing surveillance and identification of exposed cases
Can be considered when mass vaccination can not be carried out
Useful at begining and end of an outbreak

Question 44

Risk factors for poor outcome following yellow fever vaccine

Answer 44

Age over 60
Pregnancy (risk of fetal transmission- fact: mosquitos also transmit vertically)
Age under 6 months- risk of encephalitis, also means shouldn’t be given in breast feeding (Infants aged six to nine months should only be immunised following a detailed risk assessment)
Immunosupressed
HIV (can give if CD4 count over 200 and virally supressed)
No thymus (if had cardiothoracic surgery prior to 2001, or in childhood, consider as no thymus)

Question 45

T/F New medicines have black triangles for 3 years

Answer 45

F usually 5 years- can be extended

Black triangle symbolises that a medicine is under additional monitoring due to being newly licensed or has undergone significant updates

As per EMA website

Additional monitoring status is always applied to a medicine in the following cases:

it contains a new active substance authorised in the EU after 1 January 2011;
it is a biological medicine, such as a vaccine or a medicine derived from plasma (blood), authorised in the EU after 1 January 2011;
it has been given a conditional approval (where the company that markets the medicine must provide more data about it) or approved under exceptional circumstances (where there are specific reasons why the company cannot provide a comprehensive set of data);
the company that markets the medicine is required to carry out additional studies, for instance, to provide more data on long-term use of the medicine or on a rare side effect seen during clinical trials;
it is authorised with specific obligations on the recording of suspected adverse drug reactions.
Other medicines can also be placed under additional monitoring, based on advice from the Agency’s Pharmacovigilance Risk Assessment Committee (PRAC).

Question 46

T/F- Out come from encephalitis from yellow fever vaccine is poor

Answer 46

False- most recover
Unlike viscerotropic disease: 60% mortality

the reporting rate in the US is 0.8 and 0.3 per 100,000 doses for
neurological disease and viscerotropic disease respectively- this is higher for those aged over 60

Question 47

describe original antigenic sin
for which viruses does this occure

Answer 47

Bocavirus; Dengue; Influenza; Zika virus.

The basis of “original antigenic sin” requires immunological memory, and our immune system ability to autocorrect. In the context of viral infections, it is expected that if we are exposed to a native strain of a pathogen, we should be able to mount a secondary immune response on subsequent exposure to the same pathogen. “Original antigenic sin” will not contradict this well-established immunological process, as long as the subsequent infectious antigen is identical to the original one. But “original antigenic sin” implies that when the epitope varies slightly, then the immune system relies on memory of the earlier infection, rather than mount another primary or secondary response to the new epitope which would allow faster and stronger responses. The result is that the immunological response may be inadequate against the new strain, because the immune system does not adapt and instead relies on its memory to mount a response. In the case of vaccines, if we only immunize to a single strain or epitope, and if that strain/epitope changes over time, then the immune system is unable to mount an accurate secondary response. In addition, depending of the first viral exposure the secondary immune response can result in an antibody-dependent enhancement of the disease or at the opposite, it could induce anergy. Both of them triggering loss of pathogen control and inducing aberrant clinical consequences.