Intro to Vaccines + Covid

How do vaccines work

They generate an immune response in the absence of a pathogen

What do vaccines capitalize on

The generation of immune memory

What is needed when immune memory is not sufficient against rapidly invasive pathogens

Boosters

Attenuation

Reduces virulence while maintaining immunogenicity

Weakens the capability of causing a disease while still mounting an immune response

Rational attenuation

Inactivation or removal of virulence genes via targeted mutations are gene deletions

Live attenuated vaccine example

MMR

Confers lifelong immunity

Kill whole organism vaccines

Whole organisms killed by physical or chemical means

Toxoid vaccines

Antibodies are directed at toxoids neutralize exotoxins before they reach the target cells

Why are the toxoid antibodies effective at neutralizing exotoxins

They recognize linear and conformational epitopes

Subunit vaccine

Antigenic molecules or critical epitopes necessary for protection against infection

Virus like particle vaccines

Particles constructed of viral proteins that structurally mimic the native virus but lack the viral genome

Outer membrane vesicle vaccines

Contain a gram negative bacterial outer membrane region

This vaccine type contains gram negative bacteria

Outer membrane vesicle vaccine

Polysaccharide and protein polysaccharide conjugate vaccines

Need to be conjugated to proteins in order to elicit T cell dependent response and generation of immune memory

Viral vectored vaccines

Recombinant replicating or non-replicating virus with altered genomes to express the target pathogen antigen

Nucleic acid vaccines

Consist of either DNA or RNA encoding for the target antigen

SubQ or IM influence on immune response

Stimulates systemic immunity in the spleen, lymph nodes, and blood

Mucosal administration affect on immune response

Antigen stimulated lymphocytes from the initial site travel to other mucosal surfaces and confer immunity at these new sites

Passive protection

The use of specific neutralizing antibodies purified from immune donors to prevent transmission of various viruses

Herd immunity

If vaccine coverage is above the threshold for herd protection infection cannot spread in the population, making susceptible individuals indirectly protected by the vaccinated individuals

Covid characteristics

Enveloped, positive sense, single stranded, non-segmented, RNA virus

Positive sense

RNA can act as mRNA and translate into a protein

Negative sense

RNA must be converted to positive sense prior to translation

How covid enters cells

Binds to ACE2 receptors through the spike proteins then is endocytosed

Step by step covid entry into cells

ACE2 mediated binding, endocytosis, endosome, viral RNA release, translation of polypeptides, proteolysis to release the active proteins, RNA replication, translation, viral assembly at the Golgi body, and virus release

Covid adverse effects

Acute respiratory distress syndrome (ARDS) and death

The monocytes and neutrophils are attracted to the inflammation and promote more inflammation and coagulation. This results in highly inflamed and flooded lung tissue that impairs oxygen exchange and can lead to hypoxia

Four types of immunological memory that were studied in covid

Memory B cells, CD4 T cells, CD8 T cells, and antibodies

Durability

The length of time immunological memory is measured

What is IgA associated with

The respiratory system

Humoral immunity in the airways

Role of circulating T follicular helper cells

B cell help and antibody generation

Role of CCR6

Help cells move to tissues

Support the local humoral response

What does it mean that immune memory is heterogeneous

Different patterns of immunity in different people

What percent of patients retained immune memory after 6mo

95%

Step by step mRNA vaccine response

IM injection, mRNA/antigen uptake by APCs, trafficking to lymph nodes, priming of T cells, CD4 and CD8 activation, GC reaction

Viral vector vaccine

A replication defective adenovirus carrying the gene for viral spike proteins

NSAIDs cans Tylenol can be taken after vaccination, not before

How do boosters work even if they do not match the new variants

There are greater levels of cross reactivity from neutralizing antibodies

The T cells hold up well against new variants

Boosters lead to affinity maturation

What do boosters lead to

Affinity maturation

Approach to the covid vaccine development

Prototype pathogen approach

‘Plug and play’

Overlap in early clinical trials and manufacturing

FDA safety benchmarks were not lowered