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How can we design better vaccines to prevent HIV infection in women?

Rafferty H, Sibeko S, Rowland-Jones S - Front Microbiol (2014)

Bottom Line: Effective protection of women against HIV-1 infection may require a vaccine specifically targeting mucosal immune responses in the female genital tract (FGT).To achieve this goal, a much better understanding of the immunology of the FGT is needed.Advances in other fields that enhance our understanding of female genital immune correlates and the interplay between hormonal and immunological systems may also help to achieve protection of women from HIV infection.

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Medicine, University of Oxford Oxford, UK.

ABSTRACT
The human immunodeficiency virus (HIV) burden in women continues to increase, and heterosexual contact is now the most common route of infection worldwide. Effective protection of women against HIV-1 infection may require a vaccine specifically targeting mucosal immune responses in the female genital tract (FGT). To achieve this goal, a much better understanding of the immunology of the FGT is needed. Here we review the architecture of the immune system of the FGT, recent studies of potential methods to achieve the goal of mucosal protection in women, including systemic-prime, mucosal-boost, FGT-tropic vectors and immune response altering adjuvants. Advances in other fields that enhance our understanding of female genital immune correlates and the interplay between hormonal and immunological systems may also help to achieve protection of women from HIV infection.

No MeSH data available.


Related in: MedlinePlus

A general schematic of vaccine-related immune cells active at the mucosal interface of the female genital tract.
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Figure 3: A general schematic of vaccine-related immune cells active at the mucosal interface of the female genital tract.

Mentions: Timing is of the essence to achieve a protective immune response against HIV. The response must be sufficiently rapid to stop the infection before the virus disseminates, by which time it is beyond control (Haase, 2010). Systemic memory responses are too slow to prevent HIV infection at the mucosa; instead a large pool of effector cells at the FGT mucosal surface, ready for immediate mobilization, is more likely to confer protection. Direct comparison of mucosal and systemic vaccination routes has shown the mucosal route alone can induce mucosal memory populations of CTLs (Gallichan and Rosenthal, 1996) and high-avidity CTLs (Ranasinghe and Ramshaw, 2009), matching the CTL profiles of HIV controllers (Mothe et al., 2012). Systemic vaccines can elicit FGT IgG, but in comparison to mucosal vaccines induce little or no SIgA, which is produced locally by plasma cells in the FGT stroma (Nardelli-Haefliger et al., 1999; Pattani et al., 2012). Despite the dominance of the IgG subtype in the lower FGT, SIgA has a decisive role in protection, acting as the first defense against the virus by preventing attachment and hence acquisition (Neutra and Kozlowski, 2006; Brandtzaeg, 2007). Unlike IgG, IgA does not activate the complement system and so can be thought of as anti-inflammatory, important for HIV protection. The impact of a mucosal response to HIV was practically demonstrated by the success of the 1% tenofovir microbicide (Abdool Karim et al., 2010). Mucosal vaccines can also stimulate lymphatic and systemic immune responses (Belyakov et al., 1998), acting as a catch-all for virions that pass into the circulation. These factors suggest a mucosal vaccine specific for the FGT would provide the immune response most likely to prevent HIV acquisition (see Figure 3 and Box 1).


How can we design better vaccines to prevent HIV infection in women?

Rafferty H, Sibeko S, Rowland-Jones S - Front Microbiol (2014)

A general schematic of vaccine-related immune cells active at the mucosal interface of the female genital tract.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219488&req=5

Figure 3: A general schematic of vaccine-related immune cells active at the mucosal interface of the female genital tract.
Mentions: Timing is of the essence to achieve a protective immune response against HIV. The response must be sufficiently rapid to stop the infection before the virus disseminates, by which time it is beyond control (Haase, 2010). Systemic memory responses are too slow to prevent HIV infection at the mucosa; instead a large pool of effector cells at the FGT mucosal surface, ready for immediate mobilization, is more likely to confer protection. Direct comparison of mucosal and systemic vaccination routes has shown the mucosal route alone can induce mucosal memory populations of CTLs (Gallichan and Rosenthal, 1996) and high-avidity CTLs (Ranasinghe and Ramshaw, 2009), matching the CTL profiles of HIV controllers (Mothe et al., 2012). Systemic vaccines can elicit FGT IgG, but in comparison to mucosal vaccines induce little or no SIgA, which is produced locally by plasma cells in the FGT stroma (Nardelli-Haefliger et al., 1999; Pattani et al., 2012). Despite the dominance of the IgG subtype in the lower FGT, SIgA has a decisive role in protection, acting as the first defense against the virus by preventing attachment and hence acquisition (Neutra and Kozlowski, 2006; Brandtzaeg, 2007). Unlike IgG, IgA does not activate the complement system and so can be thought of as anti-inflammatory, important for HIV protection. The impact of a mucosal response to HIV was practically demonstrated by the success of the 1% tenofovir microbicide (Abdool Karim et al., 2010). Mucosal vaccines can also stimulate lymphatic and systemic immune responses (Belyakov et al., 1998), acting as a catch-all for virions that pass into the circulation. These factors suggest a mucosal vaccine specific for the FGT would provide the immune response most likely to prevent HIV acquisition (see Figure 3 and Box 1).

Bottom Line: Effective protection of women against HIV-1 infection may require a vaccine specifically targeting mucosal immune responses in the female genital tract (FGT).To achieve this goal, a much better understanding of the immunology of the FGT is needed.Advances in other fields that enhance our understanding of female genital immune correlates and the interplay between hormonal and immunological systems may also help to achieve protection of women from HIV infection.

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Medicine, University of Oxford Oxford, UK.

ABSTRACT
The human immunodeficiency virus (HIV) burden in women continues to increase, and heterosexual contact is now the most common route of infection worldwide. Effective protection of women against HIV-1 infection may require a vaccine specifically targeting mucosal immune responses in the female genital tract (FGT). To achieve this goal, a much better understanding of the immunology of the FGT is needed. Here we review the architecture of the immune system of the FGT, recent studies of potential methods to achieve the goal of mucosal protection in women, including systemic-prime, mucosal-boost, FGT-tropic vectors and immune response altering adjuvants. Advances in other fields that enhance our understanding of female genital immune correlates and the interplay between hormonal and immunological systems may also help to achieve protection of women from HIV infection.

No MeSH data available.


Related in: MedlinePlus