Targeting the mucosa: genetically engineered vaccines and mucosal immune responses

Abstract

The discovery that inoculation of DNA leads to strong and long lasting immune responses generated enthusiasm to assess the efficacy of various genetically engineered vaccines against mucosally acquired infections. Various techniques have been used to generate the most suitable DNA vaccines, ranging from immunization with naked DNA to utilizing genetically engineered recombinant viruses and bacteria to deliver the DNA. Different DNA vaccine modalities and mucosal immune responses to them have been discussed. It has been shown that even though intramuscular and intradermal immunization with these vaccines generates strong systemic responses, mucosal responses are not induced. It has been proposed that the site of immunization determines mucosal immune responses and that primed lymphocytes preferentially accumulate at sites where they have been induced thus generating the strongest cellular and antibody responses at the site of vaccination. The impact of the site of induction on mucosal immune responses to vaccines is discussed. It is possible to enhance desired vaccine effects in the mucosa and to modify the undesirable side effects. Cytokines such as IL-2, IL-12, IL-15 and IL-18 have been used to enhance CTL activity while IL-5, IL-6 and the chemokine MIP-1␣ have shown the capacity to increase IgA responses to vaccines. Genes and Immunity (2000) 1, 308-315.

Single Intranasal MucosalMycobacterium bovisBCG Vaccination Confers Improved Protection Compared to Subcutaneous Vaccination against Pulmonary Tuberculosis

“…A recent clinical study has demonstrated that, when BCG was administered mucosally to human volunteers, it preferentially induced a T-cell population expressing mucosal homing molecule ␣4␤7, which was accompanied by reduced purified protein derivative skin reactivity (12). Collectively, our present study supports the notion that airway mucosal immunization provides better immune protection in the lung upon secondary infection (16,22,23,30).…”

“…Mucosal vaccination has received increasing attention due to its potency in inducing mucosa-associated protection from mucosal infectious diseases (16,23,30). In this regard, both intragastric and intrarectal routes of TB vaccination have been explored, but it was found that not only were larger doses of vaccines required but also the protection level did not exceed that by percutaneous BCG vaccination (1,19).…”

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIVgpeRecombinant Vaccine Result in Gag-Specific CD8+T-Cell Responses in Mucosal Tissues of Macaques

“…These studies suggest that cutaneous or intramuscular immunization generates antigen-specific cells that may not travel to mucosal sites (3,11,22,32,49).…”

Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; a pilot study

“…While activated T-cells reenter lymphoid tissues and preferentially accumulate at the site of the initial activation, memory T-cells migrate continuously and randomly, similar to naive T-cells [21] [22]. The implication in terms of HIV infection is that, in the initial phase of an immune response, once primed, Ag-specific memory T-cells randomly enter and leave various lymphoid compartments but preferentially are retained in the lymphoid compartment where the antigen was presented at first [23] [24]. …”