Abstract
Although intramuscular (i.m.) administration is the most commonly used route for licensed vaccines, subcutaneous (s.c.) delivery is being explored for several new vaccines under development. Here, we use rhesus macaques, physiologically relevant to humans, to identify the anatomical compartments and early immune processes engaged in the response to immunization via the two routes. Administration of fluorescently labeled HIV-1 envelope glycoprotein trimers displayed on liposomes enables visualization of targeted cells and tissues. Both s.c. and i.m. routes induce efficient immune cell infiltration, activation, and antigen uptake, functions that are tightly restricted to the skin and muscle, respectively. Antigen is also transported to different lymph nodes depending on route. However, these early differences do not translate into significant differences in the magnitude or quality of antigen-specific cellular and humoral responses over time. Thus, although some distinct immunological differences are noted, the choice of route may instead be motivated by clinical practicality.
Highlights
The majority of licensed vaccines are administered by intramuscular (i.m.) injection, but some are approved for subcutaneous (s.c.) or intradermal (i.d.) use
We recently found that i.d. administration of an mRNA vaccine resulted in more efficient activation of antigen-presenting cells (APCs) at the site of injection compared with i.m. vaccination and was accompanied by transiently higher levels of vaccine-specific T cell responses and antibody (Ab) titers (Liang et al, 2017a; Lindgren et al, 2017)
We have previously used rhesus macaques (RMs) to explore vaccine trafficking after i.m. immunization using HIV-1 envelope glycoprotein (Env) as the model antigen (Liang et al, 2017b). We extend this to define and compare the initial events leading to vaccine responses after s.c. versus i.m. administration of another Env-based vaccine on the basis of well-ordered HIV-1 Env trimers covalently coupled to synthetic liposomes (Ingale et al, 2016; Martinez-Murillo et al, 2017; Pauthner et al, 2017) administered with or without Matrix-M adjuvant
Summary
The majority of licensed vaccines are administered by intramuscular (i.m.) injection, but some are approved for subcutaneous (s.c.) or intradermal (i.d.) use. Intramuscular administration is often preferred because it is easy to perform and generally well tolerated, with a low risk for adverse reactions at the site of injection. Administration of the yellow fever virus vaccine or influenza vaccines into the skin compared with i.m. injection results in enhanced responses in healthy individuals and, importantly, in non- or low responders (Roukens et al, 2012). We recently found that i.d. administration of an mRNA vaccine resulted in more efficient activation of antigen-presenting cells (APCs) at the site of injection compared with i.m. vaccination and was accompanied by transiently higher levels of vaccine-specific T cell responses and antibody (Ab) titers (Liang et al, 2017a; Lindgren et al, 2017)
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