Student guest post: Seasonal Flu Vaccine: Why we need it

It’s time for this year’s second installment of student guest posts for my class on infectious causes of chronic disease. Fifth one this year is by Nai-Chung Chang. 

Of the many health problems that everyone is bound to have at some point, influenza, or just “the flu,” is one of the most prominent. In fact, we call the time during which it is most prevalent the “flu season”. It has now become a regular occurrence in the U.S. to just get a shot before the flu season hits, and be free of it for the rest of the year. In some cases, like me, people just decide not to get the vaccine at all. I say to myself all the time: “It is just the flu. If I do get it, I’ll just take a nap, and I’ll be fine.” However, there are serious complications with influenza if the individual is afflicted with certain diseases, making the vaccine a necessity. Even in the general population, influenza infections could lead to serious health problems, at a lower rate, that could complicate the daily lives of individuals.

Influenza is a generic description of a variety of strains of influenza viruses, including influenza A (H1N1, H3N2), and influenza B. It is a widespread virus, and can infect both human and animals, albeit with different strains. (1) The influenza virus is difficult to completely control since it constantly undergoes different changes through antigenic drifts and shifts, small and abrupt changes in the virus constructs, respectively. (2) It causes fever, coughs, sore throat, runny nose, and a host of other symptoms that target different parts of the body. In extreme, severe cases, it may cause the death of the infected individuals. It can spread from person to person up to 6 feet away through coughing and sneezing, spraying droplets containing infectious particles into the air. The droplets either lands in the other individual’s mouth, or is inhaled into the lung. Influenza is very contagious, due to the fact that it can infect others prior to the development of symptoms, as well as a period after. In addition, there exist asymptomatic carriers that can infect others without knowing. There are vaccines provided every year prior to the start of the “flu season:” a period of time in which the population is most likely to acquire the disease. Once the symptoms develop, it can be treated with antiviral medicine, such as Tamiflu (oseltamivir) and Relenza (zanamivir).

In addition to the problems that a regular influenza infection can cause, in individuals with certain diseases, complications could develop from the interaction between the influenza virus and the disease currently affecting the patient. In asthma patients, the attacks are often triggered by respiratory virus infection, whether by the virus particle itself or the inflammation resulting from the influenza symptoms. Also, the influenza viruses could augment natural responses to allergenic particles resulting in a more severe than normal attack; influenza patients with asthma are often hospitalized as the result. (3) In patients with cardiovascular disease, influenza infections represent a high level risk. The infection could destabilize existing plaques (blocks in the artery) in atherosclerotic patients. In addition to the acute responses from the destabilization, influenza infections could also induce chronic inflammation in the body, as well as reduced clotting ability. (4) For patients with diabetes, infection with influenza represents a high risk of hospitalization and death. In diabetics, the immune system is weakened, making it difficult to fight of the disease. In addition, the infection can cause fluctuation in the level of blood sugar in the patients, through natural immune responses, or lack of desire to eat due to the effects of the influenza symptoms. There is also an increased risk of acquiring pneumonia as a complication of the infection. (5) As in the case with diabetics, patients with cancer and HIV/AIDS are also likely to have complications due to weakened immune systems from both treatment and disease.

From the variety of complications that could result from influenza infections, one can now see that it is extremely important for an individual to receive the vaccines when available. In some places, vaccines are often offered free of charge, especially in workplaces that have high exposure risks, such as hospitals and research facilities. In addition to reducing the likelihood of being affected by influenza, flu vaccines have shown to have reduced the development and progression of other diseases such as chronic obstructive pulmonary disease (COPD). (6) For individuals with HIV/AIDS, vaccines are especially important since they are more vulnerable to infections. In addition, they must be aware of the type of vaccines they are using, since certain vaccines do not work sufficiently in people with immune-deficient issues. However, there exist other treatments for the prevention of the disease, such as chemoprophylaxis, that would allow these individuals to be properly protected against possibilities of infection. (7) With the prevalence of the influenza virus in both the U.S. and globally, it is important that an individual keep up with the most current vaccines, as they are designed to combat the most common forms that would appear that flu season, since the strains changes every year.

References:

  1. CDC. Seasonal Influenza (Flu). http://www.cdc.gov/flu/index.htm
  2. CDC. How the Flu Virus Can Change. http://www.cdc.gov/flu/about/viruses/change.htm
  3. Glezen, W. Paul. Asthma, influenza, and vaccination. Journal of Allergy and Clinical Immunology 188(6): 1199-1206.
  4. Madjid M, Nagahvi M, Litovsky S, Casscells SW, Influenza and Cardiovascular Disease. Circulation 108:2730-2736.
  5. CDC. Flu and People with Diabetes. http://www.cdc.gov/flu/diabetes/index.htm
  6. Poole PJ, Chacko E, Wood-Baker RWB, Cates CJ. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews.
  7. CDC. HIV/AIDS and the Flu. http://www.cdc.gov/flu/protect/hiv-flu.htm

Student guest post: Challenges and Progresses in HIV Vaccine Research

It’s time for this year’s second installment of student guest posts for my class on infectious causes of chronic disease. Third one this round is by Jack Walsh. 

The Human Immunodeficiency Virus (HIV) infection is one of the most significant global health challenges of this 21st century. Since the isolation of the virus in 1983, it has infected 70 million people among whom 35 million have died of Acquired Immunodeficiency Syndrome (AIDS).1 Although important progresses have been made in slowing down the pandemic and reducing the morbidity and mortality related to HIV/AIDS with the highly active antiretroviral therapy (HAART) drugs, there are still difficulties in stopping the dissemination of the infection. It is estimated that for every person gaining access to HART, there are two new others infected by the virus.2 An effective and safe vaccine is therefore needed to prevent HIV from spreading, but the development of the vaccine has been proven to be an enormous scientific challenge.

HIV presents particularities that make it very difficult for researchers to find a vaccine. It is a lentivirus from the Retroviridae family, slowly progressive using an enzyme (called reverse transcriptase) for the transformation of its genome or genetic material (RNA in this case) into a new one (proviral DNA) integrated in that of the human host using another enzyme known as integrase. One of the most fascinating characteristics of the virus is its genetic variability in both an infected individual and geographically. In a same person, new mutations can be introduced in almost every new copy, creating up to millions of new particles every day. One antibody could then neutralize one virion, but not another.3 Additionally, super-infection in an individual already HIV infected results in new recombinants increasing further viral genetic diversity. The virus also presents two different types, HIV-1 worldwide and HIV-2 confined to West Africa. HIV-1 is further subdivided into subtypes or clades differently distributed on the globe and further diversified within each clade. Moreover, by integrating proviral DNA in the genome of memory cells of the immune system (CD4+ T cells) the HIV can escape the immune surveillance. To complicate the development of an effective vaccine, the virus envelope is able to hide receptor site to antibody that could potentially inhibit its effect (neutralizing antibodies). This explained the inefficiency of antibodies generated by vaccines targeting the glycoprotein 120 (gp120) located on the surface of virus developed in early vaccine trials.4

However, despite these challenges, encouraging progresses in the development of an effective HIV vaccine have been made. The first HIV vaccine trial was opened at the National Institutes of Health (NIH) Clinical Center in 1987, including 138 healthy volunteers. Other large scale trials included participants from North America and The Netherlands (1998), then Africa and Asia (1999).5 Three main approaches have been used in the development of an HIV vaccine: 1) the induction of neutralizing antibodies against HIV using the virus envelope proteins (gp120 or 140), 2) the use of viral vectors to stimulate responses form killer cells (CD8 T-cells or T cell that would recognize antigens on virus surface of the virus-infected cell, binds to it, and kill it), and 3) the optimization of cellular immunity (activation of killer cells) and humoral immunity (production of antibody) with prime-boosts (administration of one type of vaccine, such as a live-vector vaccine, followed by or together with a second type of vaccine, usually a recombinant).6 Also, to cope with the genetic variability of the virus, multiple strategies are explored, such as mixing envelope immunogens from several HIV subtypes or clades. Unfortunately, most of the tested vaccine models did not significantly reduce HIV infection in participants, except an envelope-based subunits’ vaccine tested in Thailand which showed significant decline by about 30% in HIV infection in 2009.7 Though modest, the results clearly show that HIV/AIDS is a vaccine preventable disease. More recently in 2012, a Spanish study showed promising results in the development of a therapeutic HIV vaccine effective in reducing the viral load by 90% after 12 weeks of therapy, awkwardly the vaccine lost effectiveness within a year.8 Just a few days ago, the Duke Human Vaccine Institute team published an important study, in which it has been able for the first time to map the co-evolutions of antibodies and virus in an infected individual, whose immune system launched a broad attack against the pathogen, using new technologies. They also identified the viral surface glycoprotein, which initiated the neutralizing antibody development.9

Despite two decades of disappointing results on HIV vaccine research, we now have started to see encouraging advances. For the first time a candidate vaccine was successful in significantly reducing the HIV infection. Furthermore, an important progress has been made very recently in identifying neutralizing antibodies initialization and mapping. The study provides crucial insights for the development of a vaccine that could mimic the actual antibody development and elicit non-strain specific antibodies. Progress towards finding an effective vaccine is slow, but we can optimistically say that the future is promising.

 

References

[1] World Health Organization (WHO), Global Health Observatory (GHO). HIV/AIDS, Global situation and trends. 2012. http://www.who.int/gho/hiv/en/

2 Letvin, Norman L. “Progress and obstacles in the development of an AIDS vaccine.” Nature Reviews Immunology 6.12 (2006): 930-939.

3Letvin NL. Progress Toward an HIV Vaccine. Annu. Rev. Med. 2005. 56:213–23

4Marc GP, OsmanovSK, Kieny MP. “A review of vaccine research and development: the human immunodeficiency virus (HIV).” Vaccine 24.19 (2006): 4062-4081.

5 National Institute of Allergy and Infectious Diseases (NIAID). History of HIV Vaccine Research. 2012. http://www.niaid.nih.gov/topics/hivaids/research/vaccines/Pages/history.aspx

6 Ross, Anna Laura, et al. “Progress towards development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference.” The Lancet infectious diseases 10.5 (2010): 305-316.

7 Rerks-Ngarm, Supachai, et al. “Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.” New England Journal of Medicine 361.23 (2009): 2209-2220.

8 García, Felipe, et al. “A Dendritic Cell–Based Vaccine Elicits T Cell Responses Associated with Control of HIV-1 Replication.” Science translational medicine 5.166 (2013): 166ra2-166ra2.

9 Liao HX et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature 2013. Epub April 3, 2013

Is the HPV vaccine “weak science?” (Hint: no)

Oh, Discover. You’re such a tease. You have Ed and Carl and Razib and Phil and Sean, an (all-male, ahem) cluster of science bloggy goodness. But then you also fawn over HIV deniers Lynn Margulis and Peter Duesberg. Why can’t you just stick with the science and keep the denial out?*

But no, now they’ve let it spill into their esteemed blogs. I was interested to see a new blog pop up there, The Crux, a group blog “on big ideas in science and how these ideas are playing out in the world. The blog is written by an outstanding group of writer/bloggers and scientist/writers who will bring you the most compelling thoughts throughout the world of science, the stuff most worth knowing.” Sounds ok, let’s see what stories are up…oh, one on HPV! Right up my alley. And hey, a woman! Bonus.

*Reads story*

Ohhhhh, it’s actually one on HPV vaccine misinformation, written by the author of the fawning Duesberg article referenced above. Faaantastic.
Continue reading “Is the HPV vaccine “weak science?” (Hint: no)”