Editorial
VIRAL IMMUNOLOGY Volume 28, Number 6, 2015 ª Mary Ann Liebert, Inc. P. 303 DOI: 10.1089/vim.2015.28999.dlw
A Focus on Vaccine Development David L. Woodland
T
he readers of this Journal will be well aware that vaccines are a tremendously cost-efficient medical intervention that has saved millions of lives. A case in point is measles, which can be prevented with the MMR (measles, mumps, and rubella) vaccine. This vaccine is 97% effective, and since its introduction in the United States, it has led to a 99% reduction in the incidence of this highly contagious disease. But measles is still rampant in many countries, killing many thousands of people each year. Furthermore, the disease can quickly reappear in countries where it was once controlled, as we saw in the United States last year where recent reductions in vaccination rates in some communities led to a resurgence of the disease. In the current issue of Viral Immunology, several articles specifically focus on vaccine development. The issue opens with an article by Faneye et al. that specifically addresses the problem of measles. The authors point out that measles outbreaks remain common in Nigeria despite a national immunization program. In fact, Nigeria still ranks top among countries with endemic and uninterrupted transmission of the disease. To investigate this problem, the authors analyzed anti-measles IgM antibodies from over 200 children who were either vaccinated or unvaccinated. They discovered that a large number of vaccinated children are still being infected with measles, suggesting a relatively low level of vaccine protection. However, vaccination did reduce the severity of the disease. Clearly, more needs to be done to understand the situation with this vaccine in Nigeria. Vaccines against a variety of human and animal diseases are addressed by several other articles in this issue. Jafarpour et al. point out that rotavirus infections cause severe diarrheal disease. Current vaccines against rotavirus, based on live attenuated viruses, can cause significant side effects, such as bowel obstruction, restlessness, fever, and nausea in infants. Therefore, the authors have designed a new vaccine based on computational models. They report success with a vaccine based on a new construct that is not expected to elicit side effects and which can be produced relatively cheaply in a prokaryotic expression system. A key element of most vaccines is the induction of inflammatory responses. In this regard, Gonc¸alves et al. have
evaluated the influence of human papillomavirus (HPV) vaccination on peripheral blood mononuclear cell (PBMC) proliferation and cytokine gene transcription. The authors report both proliferative PBMC responses and production of multiple cytokines in women who received the HPV vaccine. Similarly, Di Giacommo et al. have investigated the induction of humoral and cellular immune response elicited by a DNA vaccine based on the bovine herpesvirus-1 glycoprotein D with a commercial adjuvant. They show that the adjuvant significantly enhances vaccine responses in both mouse and bovine species. The last vaccine article proposes a potentially new strategy for immune evasion in hepatitis C virus (HCV) infection. The majority of infected patients develop chronic infection, suggesting that natural infection frequently leads to the development of inefficient T-cell immunity. In this regard, Samrat et al. have examined the generation and modulation of T-cell responses against HCV core proteins. A single immunization of mice with replication-incompetent recombinant adenovirus vectors expressing core antigens induces poor T-cell responses that exhibit very poor cytolytic responses. In contrast, inclusion of a toll-like receptor agonist in the vaccine elicited fully functional T cells. The authors point out that these studies are important in the investigation of prophylactic vaccine and immunotherapy strategies for HCV infection. The remaining articles in this issue of Viral Immunology investigate the role of dendritic cell-specific ICAM-3grabbing nonintegrin (DC-SIGN) in hepatitis B virus (HBV) infection. Wang et al. point out that DC-SIGN plays a key role in many viral infections, but that its role in HBV infection is unknown. The authors’ data indicate that wildtype HBV may induce insufficient activation and maturation of DCs by escaping DC-SIGN recognition through demannosylated modification. They propose that this leads to immune escape and immune tolerance for HBV infection. These findings help clarify the mechanism of HBV chronic infection and make DC-SIGN and a-mannosidase potential new targets for anti-HBV immune therapy. I thank all the authors of the articles for their excellent contributions to this issue of Viral Immunology.
Keystone Symposia on Molecular and Cellular Biology, Silverthorne, Colorado.
303
VIRAL IMMUNOLOGY Volume 28, Number 6, 2015 ª Mary Ann Liebert, Inc. P. 303 DOI: 10.1089/vim.2015.28999.dlw
A Focus on Vaccine Development David L. Woodland
T
he readers of this Journal will be well aware that vaccines are a tremendously cost-efficient medical intervention that has saved millions of lives. A case in point is measles, which can be prevented with the MMR (measles, mumps, and rubella) vaccine. This vaccine is 97% effective, and since its introduction in the United States, it has led to a 99% reduction in the incidence of this highly contagious disease. But measles is still rampant in many countries, killing many thousands of people each year. Furthermore, the disease can quickly reappear in countries where it was once controlled, as we saw in the United States last year where recent reductions in vaccination rates in some communities led to a resurgence of the disease. In the current issue of Viral Immunology, several articles specifically focus on vaccine development. The issue opens with an article by Faneye et al. that specifically addresses the problem of measles. The authors point out that measles outbreaks remain common in Nigeria despite a national immunization program. In fact, Nigeria still ranks top among countries with endemic and uninterrupted transmission of the disease. To investigate this problem, the authors analyzed anti-measles IgM antibodies from over 200 children who were either vaccinated or unvaccinated. They discovered that a large number of vaccinated children are still being infected with measles, suggesting a relatively low level of vaccine protection. However, vaccination did reduce the severity of the disease. Clearly, more needs to be done to understand the situation with this vaccine in Nigeria. Vaccines against a variety of human and animal diseases are addressed by several other articles in this issue. Jafarpour et al. point out that rotavirus infections cause severe diarrheal disease. Current vaccines against rotavirus, based on live attenuated viruses, can cause significant side effects, such as bowel obstruction, restlessness, fever, and nausea in infants. Therefore, the authors have designed a new vaccine based on computational models. They report success with a vaccine based on a new construct that is not expected to elicit side effects and which can be produced relatively cheaply in a prokaryotic expression system. A key element of most vaccines is the induction of inflammatory responses. In this regard, Gonc¸alves et al. have
evaluated the influence of human papillomavirus (HPV) vaccination on peripheral blood mononuclear cell (PBMC) proliferation and cytokine gene transcription. The authors report both proliferative PBMC responses and production of multiple cytokines in women who received the HPV vaccine. Similarly, Di Giacommo et al. have investigated the induction of humoral and cellular immune response elicited by a DNA vaccine based on the bovine herpesvirus-1 glycoprotein D with a commercial adjuvant. They show that the adjuvant significantly enhances vaccine responses in both mouse and bovine species. The last vaccine article proposes a potentially new strategy for immune evasion in hepatitis C virus (HCV) infection. The majority of infected patients develop chronic infection, suggesting that natural infection frequently leads to the development of inefficient T-cell immunity. In this regard, Samrat et al. have examined the generation and modulation of T-cell responses against HCV core proteins. A single immunization of mice with replication-incompetent recombinant adenovirus vectors expressing core antigens induces poor T-cell responses that exhibit very poor cytolytic responses. In contrast, inclusion of a toll-like receptor agonist in the vaccine elicited fully functional T cells. The authors point out that these studies are important in the investigation of prophylactic vaccine and immunotherapy strategies for HCV infection. The remaining articles in this issue of Viral Immunology investigate the role of dendritic cell-specific ICAM-3grabbing nonintegrin (DC-SIGN) in hepatitis B virus (HBV) infection. Wang et al. point out that DC-SIGN plays a key role in many viral infections, but that its role in HBV infection is unknown. The authors’ data indicate that wildtype HBV may induce insufficient activation and maturation of DCs by escaping DC-SIGN recognition through demannosylated modification. They propose that this leads to immune escape and immune tolerance for HBV infection. These findings help clarify the mechanism of HBV chronic infection and make DC-SIGN and a-mannosidase potential new targets for anti-HBV immune therapy. I thank all the authors of the articles for their excellent contributions to this issue of Viral Immunology.
Keystone Symposia on Molecular and Cellular Biology, Silverthorne, Colorado.
303
