MGY378 29: non-liv vaccines

list of non-live vax

• influenza

• Hep B

• varicella-zoster (chickenpox-shingles)

• sars2

influenza

• orthomyxovirus

• -ve ssRNA genome, 8 segments

• enveloped, HA/ NA subtypes

  • 18 HA, 11 NA genes

• 1-5 day incubation

pandemic-associated flu

influenza A

ex: bird flu

annual epidemic-associated flu

influenza B

flu-like symptoms

• cough

• fever

• URT symptoms

• headache

• myalgia (muscle pain)

• malaise (discomfort)

• 3-5 day fever

flu complications

• secondary bacterial pneumonia

• parotitis (inflammation of the parotid (salivary) glands)

• otitis media (infection or inflammation of the middle ear)

• sinusitis

• bronchitis

• encephalitis

• myocarditis (heart muscle inflammation)

• Reye’s syndrome (swelling in the liver and brain)

flu vaccines

• Salk inactivated flu vax (embryonated chicken eggs)

• IIVs

• LAIVs

• RIVs

IIVs

inactivated influenza vaxes (IIVs)

• from viruses grown in eggs

• 15ug of HA/ dose

• tri- or quadrivalent

  • 2 influenza A strains

    • H1N1, H3N2

  • 1 or 2 influenza B strains

LAIVs

live attenuated influenza vax

• quadrivalent (same strains as IIV)

  • 2 influenza A strains

    • H1N1, H3N2

  • 2 influenza B strains

• Temp-sensitive

• replicate in URT - mucosal immunity

RIVs

recombinant influenza vax

• genetically engineered baculovirus (insect virus)

• expresses recombinant HA

• insects pump out that HA and u can collect and put it into a vax

• pregnancy/ immunocompromised safe

flu and myocardial infarction likelihood

6X more likely to get heart attack after flu infection

hep B (HBV)

• partially dsDNA genome

• bloodborne/ sexually transmitted

• Risk for hepatocellular diseases increases the younger you get it

  • Infants and kids have the highest chance of getting chronic problems

  • So most parts of the world give these vax at birth

• Humans = reservoir; could be eradicated

  • But there are still lots of cases bcz of lack of vax access

first HBV vax

• Australia antigen aka HBV S-ag

• obtained ag from their blood directly

  • but HIV risk!

• 3 methods of deactivation and filtration

current HBV vax

• HBV S-ag expressed in yeast

• self-assembles into 20nm particles

• particles released by yeast cell disruption, then purified

• 6w-6month long incubation period → high antibody levels

• >25 year protection

Zoster

• varicella-zoster virus

• Initially ppl get chicken pox > latency > reactivate to shingles (zoster)

• Imm sys controls the virus and keeps it in latency in neuronal cells

• Get older > TC responses deteriorate > reactivation

• VSV reservoir = humans; could eradicate

Zostavax

• 1st zoster vax

• live attenuated

• MMR vaccine used to be MMRV

• But this live attenuated Varicella had a lot of side effects - deterred people from getting vax

• Also if u were immunocompromised/ older u cant get live attenuated vax

Shingrix

• newer, recombinant vaccine

• Generate large amount of gpE, adjuvate it, inject that

  • gpE = most abundant gp on VSVs & VSV-infected cells surfaces

• elicits gpE-specific TC response

  • memory TC for shingles protection

• generates antibody too

• works in those who have pre-existing immunity to VZV too!

phase I trials

• 20–100 healthy volunteers (or sometimes patients)

• Focus:

  • Safety

  • Side effects

  • How the drug is absorbed/metabolized

phase II trials

• 100–300 patients with the disease

• Focus:

  • Preliminary efficacy

  • Continued safety

  • Optimal dose & regimen

phase III trials

• 1,000–3,000+ patients

• Focus:

  • Definitive efficacy

  • Common side effects

  • Long-term safety

• Randomized controlled trials (RCTs) usually

phase IV

Post-Marketing Surveillance

• Purpose: What happens in the real world?

• Who: General population

• Focus:

  • Long-term effects

  • Rare or delayed side effects

  • Real-world effectiveness

• May lead to:

  • Updated guidelines

  • Warnings or even withdrawal from market if issues arise

Sars2 vaccines

all based on surface gp S-ag (spike) that virus uses for attachment, protective immunity

Pfizer & Moderna

• mRNA encoding S gene

• 3 doses

• Pfizer: 95% efficacy in phase III trial

  • good against severe disease

  • protection against infection decreases with new variants

J&J & Astrazeneca

adenoV vector expressing S gene

1 dose

Novavax

S-ag protein

2 doses

mRNA vax

• Take what ur ag is

• Generate mRNA seq of ag

• Encapsulate the mRNA into a lipid so it can enter the cell

• Cell sees the mRNA and turns it into a protein

• Protein shown to imm sys to gen imm response and gen memory

  • Good for viruses but bacteria have many protein modifications

boosters

• neutralizing abs decrease over time

  • need to increase titers → boosters

• need boosters:

  • yearly for flu

  • sars2: nAbs better match new variants

• don’t need boosters:

  • measles, mumps, rubella

  • HBV

MBC effects from vax

= memory BCs

• vax increases high-affinity virus R-binding domain-specific MBCs

• Indivs who were infected and then were vax after had hybrid immunity

• Their BCs abs were able to recog and neutralize a wider range of Sars2 variants

• Pan-coronaV vax - use more than just spike ag/ more vers of spike ag to develop a wider MBC repertoire

RSV initial vax trials

• RSV

  • severe disease in infants and elderly

  • mononegavirus → paramyxovirus (-ssRNA)

• first vax attempt

  • children had more severe disease than unvax

  • several children died

RSV mRNA vax trial

• 2023

• Phase III efficacy - randomized placebo control

• older adults

• good safety profile

• 1 dose before RSV season protects against LRTI like pneumonia

mRNA-1345 vax

• RSV

• Moderna (their 2nd mRNA vax)

• Studies in pregnant women - infants are more at risk

  • Mothers passively transfer those abs to the infant to protect it for some time during their infancy

RSV subunit vax

• subunit vax containing F protein (RSV pre-fusion protein)