News From The Journals Of The American Society For Microbiology

“Single-Shot” Vaccines May Protect Against H5N1 Influenza Virus

Two newly developed “single-shot” H5N1 influenza vaccines protected ferrets against lethal infection with the H5N1 influenza virus and may allow for mass vaccination in humans in the event of a pandemic outbreak. The researchers from Australia report their findings in the August 2009 issue of the Journal of Virology.

As the highly infectious H5N1 influenza A virus continues to persist in bird populations and infect humans through poultry, concerns of a pandemic outbreak remain high. Although human-to-human transmission has remained limited, the fatality rate among those reported human cases is greater than 60%. The threat that the virus will mutate and achieve efficient human-to-human spread emphasizes the need for effective preventative therapies.

Vaccination is considered the optimal method for controlling an influenza pandemic. Vaccines must be rapidly available to reach mass populations and they must include the minimal antigen dose (substance that promotes the generation of antibodies) to result in full immunity. The use of adjuvants (substances to improve the immune response) in vaccine development may lower the antigen dose required and ultimately ease the demand on vaccine supply during a pandemic.

Clinical trials on prepandemic vaccines containing adjuvant suggested that two injections were necessary to induce protective immunity. In this study researchers first inoculated ferrets twice with two H5N1 influenza virus adjuvant vaccines (Iscomatrix and AIPO4) and observed for protective efficacy following a lethal challenge with the H5N1 virus. Results showed that ferrets were completely protected against death and disease for at least 15 months. More significantly, a secondary study found that both adjuvant vaccines also protected ferrets from death following only a single inoculation. Specifically, ferrets receiving a single shot of the Iscomatrix adjuvant vaccine displayed fewer signs of infection and remained highly active.

“Our data provide the first indication that in the event of a future influenza pandemic, effective mass vaccination may be achievable with a low-dose ‘single shot’ vaccine and provide not only increased survival but also significant reduction in disease severity,” say the researchers.

(D. Middleton, S. Rockman, M. Pearse, I. Barr, S. Lowther, J. Klippel, D. Ryan, L. Brown. 2009. Evaluation of vaccines for H5N1 influenza virus in ferrets reveals the potential for protective single-shot immunization. Journal of Virology, 83. 15: 7770-7778.)

Infection-Causing Amoeba May be Resistant to Multiple Contact Lens Solutions

A new study suggests that some contact lens solutions do not properly disinfect against Acanthamoeba, a free-living organism in the environment that can cause a painful vision-threatening infection. The researchers from the Centers for Disease Control and Prevention, Public Health Service, and the U.S. Department of Health and Human Services, Atlanta, Georgia, report their findings in the July 2009 issue of the Journal of Clinical Microbiology.

Acanthamoeba are found in a variety of environmental sources including soil, freshwater, brackish water and seawater, as well as hot tubs and Jacuzzis. The species is associated with many different human diseases such as central nervous system infections and Acanthamoeba keratitis (AK), an infection of the cornea that can ultimately lead to blindness. 85% of AK cases in the United States are attributed to contact lens wear, with some specific risk factors being improper contact lens care and contact with nonsterile water during wear.

Insufficient anti-Acanthamoeba activity in Advanced Medical Optics Complete MoisturePlus multipurpose contact lens solution was brought to attention following a recent multistate outbreak of AK. While investigating that outbreak, researchers also compared the effectiveness of 11 other contact lens solutions against cysts of Acanthamoeba castellanii, Acanthamoeba polyphaga, and Acanthamoeba hatchetti, all of which were sample specimens collected during the outbreak. Results indicated that only the two contact lens solutions containing hydrogen peroxide showed any disinfection ability against A. castellanii and A. polyphaga after 6 or 24 hours. No significant disinfection efficacy was noted among the 11 solutions against A. hatchetti.

“The prevention of future cases of AK will require contact lens solutions that are effective against Acanthamoeba species and continued emphasis on proper lens care hygiene,” say the researchers. “Educating contact lens wearers about the risk factors for AK, including the improper use of contact lens solutions, is important; but a systematic method for evaluating contact lens solutions will reduce the chance that inefficacious solutions are available.”

(S.P. Johnston, R. Sriram, Y. Ovarnstrom, S. Roy, J. Verani, J. Yoder, S. Lorick, J. Roberts, M.J. Beach, G. Visvesvara. 2009. Resistance of Acanthamoeba cysts to disinfection in multiple contact lens solutions. Journal of Clinical Microbiology, 47. 7: 2040-2045.)

New DNA Vaccine Inhibits Deadly Skin Cancer in Mice

A new DNA vaccine inhibited malignant melanoma, a deadly form of skin cancer, in mice by eliciting antibodies that target a gastrin-releasing peptide which is known to play a key role in cancer development. The researchers from China and the U.S. report their findings in the July 2009 issue of the journal Clinical and Vaccine Immunology.

Gastrin-releasing peptide (GRP) is an important human peptide that regulates gastric acid secretion and motor function as well as elicits gastrin release. Previous research has shown that GRP plays a significant role in human cancers through atypical expression of the GRP receptor and GRP binding that activates cellular signaling and results in increased cell production and tumor formation. Anti-GRP antibodies have displayed promising antitumoral activity and DNA vaccines targeting GRP are a hopeful therapeutic approach.

In the study researchers developed a novel anti-GRP DNA vaccine including various immunoadjuvants (substances to improve the immune response) and monitored anti-GRP antibody levels in vaccinated mice. Intramuscular injections induced high levels of specific antibodies against GRP as well as suppressed the growth of melanoma cells. Additionally, researchers intravenously injected cells in the lungs and found that cells were highly diminished indicating that the vaccine may also inhibit cancer from spreading.

“In conclusion, we have demonstrated for the first time that immune responses which are elicited by a novel anti-GRP DNA vaccine suppress the proliferation and growth of melanoma tumors in mice,” say the researchers. “The antiangiogenesis and antimetastastic activities of this DNA vaccine suggest a novel approach against various cancers, especially malignant melanoma.”

(J. Fang, Y. Lu, K. Ouyang, G. Wu, H. Zhang, Y. Liu, Y. Chen, M. Lin, H. Wang, L. Jin, R. Cao, R.S. Roque, L. Zong, J. Liu, T. Li. 2009. Specific antibodies elicited by a novel DNA vaccine targeting gastrin-releasing peptide inhibit murine melanoma growth in vitro. Clinical and Vaccine Immunology, 16. 7: 1033-1039.)

Source:
Carrie Slijepcevic

American Society for Microbiology