Questions & explanations
1. In a branching process, if each infected person on average infects 2 others (R0=2), what is the chance the outbreak eventually dies out?
In a branching process with R0=2, the probability of extinction is the solution to the equation p = (1/2)^p? Actually, for a simple Poisson branching process, the extinction probability is the smallest root of the generating function. For R0=2, the extinction probability is 0.5 if the offspring distribution is geometric? Wait, let's be accurate: For a Poisson distribution with mean 2, the extinction probability is about 0.203. But a common example: if each case produces exactly 2 secondary cases, then the outbreak never dies out. In reality, we use a distribution. So the chance depends on the distribution. Generally, if R0>1, there is still a chance of extinction, especially if the initial cases are few.
2. Describe an evolutionary consideration when designing a phage therapy treatment.
One important consideration is the trade-off between phage virulence and bacterial resistance. A phage that kills bacteria very quickly may put strong pressure on bacteria to evolve resistance. A phage that kills more slowly might allow the immune system to help clear the infection. Also, phages can evolve during treatment, so we need to anticipate how they might change. For example, phages might evolve to become less effective if they mutate. Another consideration is that phages can carry genes that make bacteria more harmful, so we must choose safe phages. Finally, we should consider the bacterial population structure at the infection site, as different environments may favor different phage traits.
3. Compare the approaches for leishmaniasis vaccines with those for malaria vaccines.
Both leishmaniasis and malaria are parasitic diseases transmitted by insects (sand flies and mosquitoes, respectively). Malaria vaccines, like the RTS,S vaccine, are subunit vaccines that target the parasite's surface proteins. Similarly, leishmaniasis subunit vaccines target specific parasite antigens. Both diseases have complex life cycles, and vaccines need to induce strong T-cell responses. However, Leishmania parasites live inside cells, while malaria parasites have a blood stage, so the immune targets differ. The success of the malaria vaccine provides hope, but leishmaniasis vaccine development faces additional challenges due to the parasite's ability to hide in immune cells.
4. Compare the evolutionary dynamics of a virus in a single host versus between hosts.
Within a single host, the virus evolves in response to that host's immune system and treatments. The population size is limited to the cells of that host. Between hosts, the virus faces different immune systems and may need to adapt to new environments, like different tissues or transmission routes. Intra-host evolution often involves rapid mutation and selection for immune escape. Inter-host evolution selects for traits that help the virus spread to new people, such as stability in the air or ability to infect new cell types. The timescale is also different: intra-host changes happen over days to years, while inter-host evolution occurs over transmission chains and longer periods.
5. Compare the evolutionary pressures on an oncolytic virus inside a tumor versus in normal tissues.
Inside a tumor, the virus faces a unique environment: cancer cells divide rapidly, have abnormal signaling, and often suppress immune responses. The virus evolves to exploit these features for efficient replication. In normal tissues, the virus encounters healthy cells with intact defense mechanisms and a strong immune response. If the virus mutates to better infect normal cells, it could become dangerous. Therefore, the virus is under pressure to stay specialized for cancer cells. However, if the virus spreads to normal tissues, it may evolve to adapt there, losing its oncolytic specificity. This is why careful monitoring and engineering are needed to maintain tumor selectivity.
6. Compare the goals of an HSV vaccine with those of an HPV vaccine.
Both HSV and HPV vaccines aim to prevent sexually transmitted infections that cause significant health problems. The HPV vaccine is very effective at preventing infection with high-risk HPV types that cause cervical cancer and genital warts. It is a prophylactic vaccine given to preteens before they become sexually active. An HSV vaccine would similarly aim to prevent genital herpes, but it also needs to address oral herpes. Unlike HPV, HSV establishes lifelong latency and can reactivate, so a therapeutic component may be needed. The success of the HPV vaccine shows that preventing viral infections through vaccination is possible, but HSV presents unique challenges.
7. Compare the EBV vaccine approach to the vaccine for another herpesvirus like varicella-zoster (chickenpox).
Both EBV and varicella-zoster virus (VZV) are herpesviruses that cause lifelong infections. The chickenpox vaccine is a live attenuated virus that prevents primary infection and has been very successful. For EBV, most vaccine candidates use only parts of the virus (subunit vaccines) rather than a live virus, because safety concerns are higher. The chickenpox vaccine also reduces the risk of shingles later in life, similar to how an EBV vaccine might reduce cancer risk. However, EBV infects different cells and has a more complex immune evasion, making vaccine design harder. The success of the chickenpox vaccine gives hope that an EBV vaccine is possible.
8. Why do many viruses target the interferon system, and what is a common weakness in this strategy?
The interferon system is a first line of defense that can quickly stop viral replication. By blocking interferon production or signaling, viruses gain time to replicate before the immune system fully activates. However, this strategy often relies on specific viral proteins that may be recognized by the immune system. Also, if the virus blocks one part of the interferon pathway, the host may use other pathways to still produce an antiviral state. For example, some viruses cannot block all types of interferons. Additionally, mutations in the viral proteins can reduce their effectiveness. So while targeting interferon is common, it is not always perfect.
9. Compare the approach for a schistosomiasis vaccine with that for a hookworm vaccine.
Both schistosomiasis and hookworm are parasitic worm infections that affect millions of people in tropical areas. Both vaccines aim to prevent infection or reduce worm burden. Hookworm vaccine candidates often target proteins that the worms use to feed on blood, while schistosomiasis vaccines target proteins on the worm's surface. Both diseases have complex life cycles and require vaccines that induce strong antibody responses. However, schistosomiasis worms live inside blood vessels, while hookworms live in the intestine, so the immune targets differ. Both fields are actively researching subunit vaccines, and progress in one can inform the other.
10. Why might a virus that inhibits apoptosis also need to prevent inflammation?
When a cell dies by apoptosis, it usually does not cause inflammation because the cell contents are neatly packaged. But if the virus blocks apoptosis, the cell might later die by necrosis, which spills contents and triggers inflammation. Inflammation brings immune cells to the site, which can attack the virus. So many viruses that block apoptosis also have ways to reduce inflammation. For example, some viral Bcl-2 homologs also interfere with pathways that produce inflammatory signals. By controlling both cell death and inflammation, the virus avoids alerting the immune system. This dual strategy helps the virus stay hidden and replicate longer.
11. How does a killed leishmaniasis vaccine work compared to a live attenuated one?
A killed leishmaniasis vaccine contains whole Leishmania parasites that have been inactivated (killed) so they cannot cause disease. When injected, the immune system sees the dead parasites and learns to recognize them, creating memory cells. A live attenuated vaccine contains live parasites that have been weakened so they do not cause illness but still multiply a little. This often triggers a stronger and longer-lasting immune response because the live parasites mimic a natural infection. However, live attenuated vaccines carry a small risk of causing disease in people with weak immune systems. Both types aim to protect against future infection.
12. How can oncolytic viruses evolve to become less effective against cancer?
Oncolytic viruses can evolve mutations that reduce their ability to infect cancer cells or replicate inside them. For example, if the virus relies on a specific receptor to enter cells, cancer cells might stop making that receptor, making the virus unable to attach. The virus might also evolve to replicate more slowly, giving the immune system time to clear it. Additionally, the virus could mutate to become less toxic to cancer cells, allowing them to survive. The host's immune response can also drive evolution by selecting for viruses that are less visible to immune cells, but that might also make them less effective at killing cancer.