The Heterogeneity of B-cell Memory and Vaccine Design

The establishment of long-term humoral memory to a pathogen is an important goal of vaccination. One of the important component of it is belong to memory B cells. This cells will help us from the future re-attack of pathogens by surveying their specific antigen in the periphery for affinity maturation. Classically the marker for B cell memory was expressed by CD27. However recent finding suggest the heterogeneity of the memory compartment that involving CD27- memory B cells. If a vaccine has been designed to non-specific memory B cell, it potentially will result in loss of maintenance and/or establishment of an important subset of memory populations. Consequently, this will lead to improper localization and ineffective response that result in loss of vaccine efficacy. Therefore it would be challenging to study the environment that create this subset memory cells and to understand their property in vivo for the better vaccine design.

Reference:
http://www.frontiersin.org/b_cell_biology/10.3389/fimmu.2011.00077/full

Vaccinations for Cancer

For the past several decades, countless studies of been conducted in hopes to finding a vaccine that will allow our immune system to recognize carcinogenic cells and destroy them. Though the FDA still not yet approved most of them them, numerous clinical trials are currently in progress. As of now there are two main types of cancer vaccinations. The first type is Preventative vaccines which are intended for health individuals with no cancer and the second type are Treatment vaccines intended for individuals with already existing cancer. These sets of vaccination belong to a class of medication called Biological Response Modifiers where the ultimate goal is to stimulate and restore the body’s ability to fight off infections. At first researchers thought that similar to other vaccinations like Measles and Mumps, the vaccination would allow the immune system to recognize specific cancerous cell thus preventing infection, but because carcinogenic cells mutate so rapidly it is impossible to create a good response vaccine. This is where Preventative vaccinations come into play. Instead of targeting cancerous cells, these vaccinations target viruses, bacterium, and parasites that lead to cancer.

As of now, the U.S. Food and Drug Administration has only approved two preventative vaccinations Gardasil and Cervarix, these two vaccines are used to prevent two types of Human Papillomavirus (HPV) which causes about 70% of all cervical cancer cases worldwide. Protecting against HPV may also prevent vulvar, vaginal, anal, and oropharyngeal cancers. Other types of targeted organisms include Hepatitis virus B & C which can cause various types of liver cancers, helicobacter pylori a bacterium that causes stomach cancer and parasites such as schistosomes which causes bladder cancer. Visit site

http: //www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines to see full list.

Lastly, there are the treatment vaccines used to treat patients that are already diagnosed with cancer. These are sometimes called True Cancer Vaccines and are only specific from person to person. They are meant to trigger a person’s own specific response in which the body will then attack cells with one or more specific antigens. The goal of these vaccines is to delay or stop cancer cell growth causing the tumor itself to shrink and prevent the cancer from coming back into the system. Last year, FDA has approved the first cancer treatment vaccine called Provenge. This vaccine is made for men with metastatic prostate cancer and is designed to stimulate an immune response to prostatic acid phosphatase (PAP) which is an antigen found in prostate cancer cells. Since this treatment is specific from patient to patient, how the vaccination process works is first white blood cells are extracted from the patient and exposed to PAP. Then, the white blood cells are infused back to the patient via vein. This process is repeated two more times, two weeks apart. The goal is to stimulate an immune response to recognize the PAP antigen. So far, this clinical trial shows good response.

Sources:

http://www.cancer.org/Treatment/TreatmentsandSideEffects/TreatmentTypes/Immunotherapy/immunotherapy-cancer-vaccines

http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines

Murphy KM, Travers P, Walport M, editors. Janeway's Immunobiology. 7th ed. New York: Garland Science, 2007

Understanding Structural Characteristic of Virus Neutralization to Develop Universal Vaccine for Influenza

Deal with the flu is tricky because the virus keep changing its surface proteins by genetic reassortment or drift. Influenza Vaccine made last year might not effective anymore today. That’s why that human can be infected over and over again during the lifetime. This is become a challenges for us to develop what so called “Universal Vaccine for Influenza”.

Now, the big question is how we are going to do that?

One way is by understanding the structural characteristic of human immune system. That is, at least now I understand why it is important to understand the very detail of anatomy and function of antibodies. So, let me step into the detail of it by put what we have learned so far from our class into the context of influenza case.

So far, we have learn that antibody have hypervariable region called Vl (for the light chain) and Vh (for the heavy chain). There are also CDR (Complementary Determining Region) which determine the specificity of each antibody to antigen. We believe also that the antibody have million preexisting “types” to anticipate whatever kind of pathogen molecular structures. But perhaps that won’t works for influenza viruses?

There are 16 antigenically different HA subtypes and 9 antigenically different NA subtypes of influenza viruses. The combination of these two components define all known existing subtypes of Influenza A viruses.

Now, the problem is how our antibody system could provide a rather broad strain protection, than only targeting the HA surface antigen of the viruses, which capable for changing rapidly to avoid and escape from our immune system.

One way to study how our immune system can protect us is to study the how antibody that the survivor of a novel influenza infected person works on preventing from fatal condition.

There is a clue that the antibody of the survivor have a broad protection of flu viruses which might involve a specific region HA2 which is located at the stem or stalk of the HA protein, not at the head!. The HA1 region at the head is believe as a decoy for influenza viruses to escape from neutralization. So, it is suggested that vaccine developer should re-focus on Broad Neutralizing Antibodies (BnAb) that targeting hydrophobic stem region of HA2 and inhibit fusion process, which showed to be cross reactive for multiple viruses, rather then focus on antibody that works on HA1 epitopes. Do you believe that?

Reference:

Han, T. and W. A. Marasco "Structural basis of influenza virus neutralization." Ann N Y Acad Sci. 2011 Jan, 1217: 178-90.

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