Lecture 23 Flashcards
1
Q
Influenza
A
- Flu lineages named for their surface proteins
- Key Surface Proteins:
- HA hemagglutinin: principal antigen recognized by immune response
- NA neuraminidase: allows escape from host cell and spread throughout body
- Seasonal viruses: H1N1, H3N2
- Bird flu viruses: H5N1, H7N9
- Zoonotic flu: caused by influenza viruses that occur naturally in wild animals. Don’t occur in humans -> humans unlikely to have immunity
- Pandemic flu: novel human flu viruses that cause global outbreaks of serious illness. Little natural immunity, so disease spread easily from person to person
- Seasonal flu: Flu viruses that circulate regularly in human populations. Many people have immunity and vaccines are available
2
Q
H5N1: Bird flu
A
- Nearly every case involves close contact with infected birds
- H5N1 and other subtypes have caused spillover infections in humans, but not good at transmitting human to human
- Fear that one of these viruses evolve to be better transmitted between humans
3
Q
Categories of influenza
A
Zoonotic flu -> (viral evolution to transmit better between humans) -> pandemic flu -> (viral evolution to evade effects of immunity) -> seasonal flu
4
Q
Modes of evolution of influenza
A
- Most evolution in seasonal flu is brought about by accumulation of many small mutations (antigenic drift)
- Occasionally, major reassortment occurs where whole RNA segments are transferred from one strain to another
5
Q
Evolution of pandemic strains
A
- Many but not all pandemic flu strains are result of reassortment between human infecting and animal infecting strains
- Reassortment requires two viruses to both infect the same cell
- Since flu viruses use machinery of host cells to replicate, co-infection of a single cell can result in production of viruses that contain genetic parts of both parent viruses
- After each past pandemic, pandemic strain circulates seasonally in human populations replacing previously circulating seasonal strain or reducing its prevalence
6
Q
Immunity to influenza
A
- Most individuals recover from flu and are thought to maintain some immunity to that particular strain
- Evidence: 1977re-emergence of genetically identical variant of H1N1 strain, majority of illness occurred in people under age 20, older people retained immunity
7
Q
Why is influenza still a problem every year
A
- Continuous evolution of antigenic sites on hemagglutinin protein (HA)
- Continuous nucleotide substitutions
- Most seasonal flu strains go extinct
- Recent flu strains are descended from a single ancestor
8
Q
Immunity to influenza
A
- Most individuals recover from flu and are thought to maintain long lasting immunity to particular strain
- Cross immunity between strains is relatively weak, meaning immune response generated to one influenza strain may offer little protection against antigenically different influenza strains
9
Q
Evaluating cross-immunity in influenza
A
- Experiment: vaccinate horses with a particular flu strain then challenge them with same or different strains
- Result: Horses more likely to get infected by viruses that were more genetically/antigenically different than vaccine strain and their infections lasted longer
10
Q
Vaccines for influenza
A
- WHO gathers information on circulating strains and epidemiological trends in dozens of countries and updates vaccines each year to best match these data
- New strains are tested against existing vaccines to determine whether they will induce satisfactory antibody levels in human sera
- Takes about 6 months to create seasonal influenza vaccine
11
Q
Making flu vaccines
A
- Inactivated influenza virus vaccines are cultured in chicken eggs or cell culture and produced according to recommendations of the WHO each year
- Inactivation is achieved through damage to viral nucleic acid by chemical treatment or radiation
- Vaccination of people not at high risk of influenza mortality helps to control infection rates through herd immunity
12
Q
Vaccines
A
- Vaccines are biological treatments meant to improve immune responses to future exposures to specific diseases
- Antigens in vaccine prime the immune system so that it responds quickly to future assaults by same antigens
- Making vaccines is an evolutionary process
13
Q
Evolution in a vaccinated world
A
- Antibiotics are failing with increasing frequency due to evolutionary responses
- Immune systems are sources of massive selection on pathogens
- By activating an immune response, vaccination can be viewed as a potential source of selection on pathogens
14
Q
Hepatitis B virus
A
- Globally significant cause of hepatitis, liver cirrhosis, and liver cancer
- Vaccine targets “a “ determinant
- In 1990s, there was a concern of vaccine resistance: large clinical trial found a number of vaccinated individuals ultimately acquired infections
- These infections are caused by a vaccine resistant mutant
- Mutant allele increased in frequency in vaccinated people
- Thus HBV populations are evolving in response to vaccine
- Vaccine resistant strains not a major health problem -> health benefits of vaccination have continued
- Mutant strains are outcompeted in unvaccinated hosts (cost to vaccine resistance)
15
Q
Malaria
A
- Two vaccines approved for use: RTS, S and R21
- Both target CSP antigen
- Lot of existing variation in CSP
- Trials suggest non-vaccine alleles rapidly increase in frequency
- Efficacy of these vaccines is much less than for vaccines against other diseases
16
Q
Can vaccines alter course of evolution of their targets
A
- Evolution occurs through mutation to new non-vaccine strains, sorting of existing strains, favoring the nonvaccine strain
- Evolutionary consequences may not always be bad (non-vaccine strain might be less virulent) and epidemiological consequences may still be positive
17
Q
Evolution in a vaccinated world
A
- Vaccination is one of the great advances of human health
- Vaccination can drive the evolution of pathogens
18
Q
Emergence and evolution of SARS-CoV2
A
- Zoonotic -> (viral evolution to transmit better between humans) -> pandemic
