Th Cell Proliferative Responses Research Articles

Macrophage inflammatory protein‐1α expression plasmid enhances DNA vaccine‐induced immune responses against HSV‐2

In this study, we examined the effectiveness of macrophage inflammatory protein (MIP)-1alpha cDNA as a HSV-2 DNA vaccine adjuvant. pcDNA3-gD (pgD) and pcDNA3-MIP-1alpha (pMIP-1alpha) were co-injected to examine the modulatory effects of MIP-1alpha on immune phenotype and protection against lethal challenge with HSV-2. We found that Th-cell proliferative responses were dramatically enhanced by co-injection of pgD and pMIP-1alpha compared with injection of pgD alone. The secretion of IL-2 and IFN-gamma was also significantly increased by pgD and pMIP-1alpha co-injection; however, the production of cytokines IL-4 and IL-10 was not affected by co-injection. pgD and pMIP-1alpha co-injection resulted in a moderate enhancement of systemic gD-specific antibody level, but mucosal secretory IgA was markedly enhanced. When BALB/c mice were challenged intravaginally with 100 LD50 of HSV-2 strain Sav, pMIP-1alpha co-injection with pgD improved their survival rate and significantly reduced both the number of mice with lesions and the lesion severity. Therefore, MIP-1alpha cDNA as a HSV-2 DNA vaccine adjuvant drives antigen-specific Th1-type responses, reducing HSV-2-derived morbidity and mortality.

Age-Related Development of Human Memory T-Helper and B-Cell Responses toward Parainfluenza Virus Type-1

Human parainfluenza-1 virus (hPIV-1) infections are a major cause of respiratory illness in young children. While children and adults are each susceptible to hPIV-1 infection, the clinical symptoms in adults are mild and hospitalizations are rare. One explanation for the differences in disease severity is that immune memory responses are simply inferior in children as compared to adults and cannot counter virus growth. Alternatively, it has been suggested that immune (particularly T-helper (TH) cell) responses toward respiratory viruses are superior in children versus older individuals, and that these responses contribute to, rather than protect from, disease symptoms. As a test of these possibilities, we analyzed hPIV-1-specific T-helper (TH) and B-cell memory responses among individuals of various ages, including children hospitalized with hPIV-1-induced croup. Experiments revealed: (1) hPIV-1-specific B-cell and class-II restricted TH-Cell proliferative responses were present in all tested adults. (2) TH-cells responded to internal viral proteins as well as to the external glycoprotein, hemagglutinin-neuraminidase. (3) Immune responses were highly cross-reactive with Sendai virus. (4) Memory B-cell and TH-cell responses were extremely poor in young children, inclusive of children tested upon hospital entry for hPIV-1-induced croup. In total, results did not support the theory that naturally induced hPIV-specific memory responses cause respiratory illness. Rather, results showed a correlation between memory and a good clinical outcome and highlighted Sendai virus as a strong candidate for an hPIV-1 vaccine.