Immunology: (Concepts of) Vaccination

Impact on human and animal health

Why it matters: reduced infectious disease, animal suffering and mortality; improved food security; potential reductions in antimicrobial use.

vaccines have transformed public health

since national programmes for immunization first became properly established and coordinated in the 1960s.

Saved ~4 million human lives per year

• More than halved childhood mortality

• Multi £billion increases in farming productivity

• Key strategy against antimicrobial resistance

welfare and economic benefits

Vaccine schedules

Core vaccines

Recommended in a population because of disease severity, prevalence, zoonotic importance or risk

Non-core vaccines

Selected according to lifestyle, geography, exposure and individual circumstances

what do vaccines prevent from

Even when vaccines fail to prevent infection they can have benefit

vaccines can protect the unvaccinated

vaccination threshold must be met to actually be affecting

origins of vaccination

variolation

what’s in a vaccine today?

Antigen: the molecular target recognised by

antigen-specific B- and T-cell responses

Adjuvant: a component added to some vaccines

to enhance or shape the immune response

(aluminium salts, oil emulsions, saponin-based)

Formulation: the vaccine’s overall composition,

including components that support antigen stability

or delivery

how do vaccines work?

Vaccines expose the immune system to antigens in a controlled way, inducing protective immune responses and immunological memory.

Important outcomes

• Long-lived plasma cells maintain antibody production

• Memory B cells enable accelerated antibody responses

• Memory T cells enable accelerated helper or effector responses

how does immune memory protect us?

Pre-existing immunity

Long-lived plasma cells maintain antibodies that can prevent infection or disease immediately

Immunological recall

Memory B and T cells generate faster responses after re-exposure, potentially limiting pathogen replication and disease

Protection can depend on antibodies already present, on immune recall, or on both.

how vaccination generates immunity

4 stages

in the next slides

key immune cells in vaccination

Dendritic cells: acquire antigen and activate naive T cells

CD4 T cells: recognise peptide–MHC II and coordinate immune responses

CD8 T cells: recognise peptide–MHC I and can kill infected cells

B cells: recognise antigen and can differentiate into antibody-secreting or memory cells

Plasma and memory cells: maintain antibodies or provide accelerated responses after re-exposure

administer vaccine

vaccine antigen taken up by DCs

anitgen promotes danger singlas recognised by PRR to help activate it

processed into peptides and taken up MHC class II

2) DC present these peptides to activate antien specific T cells - e.g. CD4 T T cells and CD8 on MHC I depends

3) if CD8 cell then becomes effector and memory cells they are basically cytotoci T cells

if CD4 T ce;; gives B cell production cytokines to activate other cells - at the same time B cells can recognise BCR on antigen from vaccine l ike an antibody then basically proliferates and matures

some vaccines not vet good generating T cell responses

vaccination routes and immunity

Injectable: intramuscular (IM) or subcutaneous (SC) Often strong systemic antibody and immune-memory responses

Mucosal: intranasal, oral, spray Can favour immunity at mucosal surfaces, including local (IgA) antibodies and tissue-resident cell responses

Route selection depends on the required immune response and practical delivery considerations.

• Intranasal: selected canine respiratory vaccines; live influenza vaccine in children

• Oral: wildlife rabies bait; oral polio vaccine in people

• Spray or drinking water: selected poultry vaccines

what is important for protection? correlates

• Correlate of protection (CoP) = a measurable immune marker that statistically predicts protection

• Majority of known CoPs are antibody (ELISA etc)

mainly human vaccines loads same for animals antibodies in the pic

what is important for protection

Systemic antibodies, including IgG

Can protect against pathogens or toxins in blood and tissues

Mucosal antibodies, particularly secretory IgA Can help prevent pathogen establishment at mucosal surfaces

Tissue-resident memory T cells

Can mount rapid local cellular responses

waht is important for protection? over time

y axis contribution to proection - higher better

x axis period of time

TRM = Tissue resident - they are very effective initially but weaken over time

T cell needs activation

antibody usually already there

immune response - durability is very big factor cos decreases over time

designing a protective vaccine

why are some vaccines less effective?

1. Incomplete protection

Vaccination may reduce disease but not

prevent infection or transmission

Example: porcine reproductive and respiratory

syndrome virus (PRRSV)

2. Antigenic variation

Strains may differ in recognition by vaccineinduced immunity

Example: influenza (human, equine, avian);

infectious bronchitis virus

3. Insufficient durability

Protective immunity may decline and need

repeat vaccination

Example: some leptospirosis vaccines

4. Host or implementation factors

Maternal antibody in young animals, poor

health, incorrect storage or administration,

incomplete courses

Vaccine effectiveness depends on the pathogen, host, vaccine and how it is used.

vaccination innovation: solving issues - the brackets are just examples

• Poor immunity (Leptospira bacterins, parvovirus vaccines)

• Non-sterilizing immunity (Acellular pertussis, PRRSV)

• Pathogen-escape: (seasonal Influenza, infectious bronchitis virus)

• Insufficient durability (SARS-CoV-2, Leptospira bacterins)

• Antibodies enhanced disease (feline infectious peritonitis, RSV)

• Distribution challenged e.g., cold chain (early mRNA COVID-19)

• Vaccine interferes with serodiagnosis (DIVA) (FMDV)

live vaccines

Mechanism: a live vaccine organism can replicate or persist

sufficiently to stimulate immune responses

Advantages: often induces strong and durable humoral and

cellular responses

Limitations: replication-related safety considerations, possible

interference by pre-existing immunity, and storage requirements

Examples

• Human: measles–mumps–rubella (MMR), yellow fever

• Veterinary: modified-live canine distemper and parvovirus;

attenuated CVI988/Rispens and naturally avirulent HVT (Marek’s

disease)

inactivated vaccines

Mechanism: whole pathogens are rendered non-infectious while

retaining relevant antigenic structures

Advantages: cannot replicate or revert to virulence

Limitations: often require adjuvants and repeated doses;

cellular responses may be less prominent, depending on

formulation

Examples

• Human: inactivated polio (IPV), hepatitis A, rabies

• Veterinary: foot-and-mouth disease, leptospirosis bacterins, rabies

toxoid and subunit vaccines

Toxoid vaccines: contain inactivated bacterial toxins and induce

toxin-neutralising antibodies (e.g. tetanus vaccines for horses

and people)

Subunit vaccines: contain selected pathogen antigens rather

than whole organisms (e.g. porcine circovirus type 2 capsid in

pigs; hepatitis B and HPV in people)

Shared considerations: antigen selection is critical; adjuvants

and repeat doses may be needed

vectored and nucleic acid vaccines

Viral-vectored: a viral vector delivers a gene encoding the target antigen (e.g. canarypox-vectored equine influenza; adenovirus-vectored COVID-19 vaccines)

DNA and RNA: genetic instructions enable host cells to produce the antigen (e.g. DNA vaccine against infectious haematopoietic necrosis in salmon; mRNA COVID-19 vaccines)

Advantages: antigen made inside host cells can support both humoral and

cellular responses

Limitations: performance depends on the vector or delivery system, existing

immunity to the vector, the host and manufacturing requirements

comparing vaccine platforms - basically what he said

Vaccine safety: benefits and risks

• Most veterinary vaccines have favourable benefit–risk profiles when used

appropriately

• Local reactions and transient systemic effects may occur; serious reactions

are uncommon

• Some live vaccines have specific contraindications, including in particular

pregnant or immunocompromised animals

• Vaccine use must follow product-specific authorisation and safety

instructions

• Suspected adverse events, including lack of efficacy, should be reported (in

the UK, to the Veterinary Medicines Directorate, VMD)

enhanced disease after vaccination

Antibody-dependent enhancement (ADE)

• Antibodies enhance infection, e.g. Fc

receptor-mediated uptake of virus into

macrophages

• Veterinary: experimental feline coronavirus

(FIP) studies

• Human: dengue, on infection with a

different serotype

Vaccine-associated enhanced disease (VAED)

• More severe disease on infection after

vaccination; broader than ADE

• Can involve non-neutralising antibody,

immune complexes and skewed T-cell

responses

• Human: formalin-inactivated RSV vaccine

(1960s); veterinary: inactivated bovine RSV

vaccines in experimental calf studies

DIVA: infected or vaccinated?

DIVA = Differentiating Infected from Vaccinated Animals

Vaccination may complicate serological surveillance because both infection and vaccination can induce antibodies

Example: infectious bovine rhinotracheitis (IBR), caused by bovine herpesvirus 1 (BoHV-1)

DIVA strategies can support surveillance and eradication programmes while vaccination continues.

Deploying vaccines: issues

• Poultry industry – 74% meat and 68% eggs are produced under intensive production conditions

• Control of infectious diseases critical in houses containing >20,000 birds

• Conventional approaches to vaccinating chickens via needle inoculation not practical

• Delivery through feed/drinking water or spraying requires boosters & not cost-effective

vaccination innovation: delivery

• In ovo vaccination against Marek’s disease (herpes virus) shown to be effective

• Capable of introducing several antigens simultaneously into >50,000 eggs/hour

• Earlier onset of immunity, uniform & fast delivery, reduced stress and labour costs

effective vaccines need effective vaccination programmes

Even good vaccines work best within comprehensive control:

• High population coverage

• Surveillance and diagnosis

• Biosecurity and movement control

• Understanding of the epidemiology

• Community awareness and vaccine uptake

take - home messages