Salivary human immunodeficiency virus (HIV)-1-specific immunoglobulin A in HIV-1-exposed infants in Kenya

Farquhar, Carey; VanCott, Thomas C.; Bosire, Rose; Bermúdez, Cimara; Mbori‐Ngacha, Dorothy; Lohman-Payne, Barbara; Nduati, Ruth; Otieno, Phelgona; John‐Stewart, Grace

doi:10.1111/j.1365-2249.2008.03664.x

Cited by 20 publications

(23 citation statements)

References 32 publications

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“…The ability to effectively stimulate antigen-specific IgA in saliva could be helpful in preventing multiple diseases such as dental carries (11), or for stopping transmission of HIV from infected mother to child via breast feeding (9, 10). …”

Section: Discussionmentioning

confidence: 99%

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Vaccine Delivery to the Oral Cavity Using Coated Microneedles Induces Systemic and Mucosal Immunity

Tao

Krebs

et al. 2014

Pharm Res

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Purpose The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses. Method Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner lower lip and dorsal surface of the tongue of rabbits. Histology was used to confirm microneedle insertion, and systemic and mucosal immune responses were characterized by measuring antigen-specific immunoglobulin G (IgG) in serum and immunoglobulin A (IgA) in saliva, respectively. Results Histological evaluation of tissues shows that coated microneedles can penetrate the lip and tongue to deliver coatings. Using ovalbumin as a model antigen it was found that the lip and the tongue are equally immunogenic sites for vaccination. Importantly, both sites also induced a significant (p < 0.05) secretory IgA in saliva compared to pre-immune saliva. Microneedle-based oral cavity vaccination was also compared to the intramuscular route using two HIV antigens, a virus-like particle and a DNA vaccine. Microneedle-based delivery to the oral cavity and the intramuscular route exhibited similar (p > 0.05) yet significant (p < 0.05) levels of antigen-specific IgG in serum. However, only the microneedle-based oral cavity vaccination group stimulated a significantly higher (p < 0.05) antigen-specific IgA response in saliva, but not intramuscular injection. Conclusion In conclusion, this study provides a novel method using microneedles to induce systemic IgG and secretory IgA in saliva, and could offer a versatile technique for oral mucosal vaccination.

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Section: Discussionmentioning

confidence: 99%

“…Thus, oral mucosa is a potential site to induce secretory immunoglobulin A (sIgA) in the saliva. The potential clinical translation of inducing sIgA in saliva could be to prevent HIV transmission from mother to newborns during breastfeeding (9, 10) or to prevent dental caries (11). …”

Section: Introductionmentioning

confidence: 99%

Vaccine Delivery to the Oral Cavity Using Coated Microneedles Induces Systemic and Mucosal Immunity

Tao

Krebs

et al. 2014

Pharm Res

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“…However, other studies have reported little or no evidence of HIV-specific mucosal IgA responses in HIV-exposed uninfected subjects (12,37). Furthermore, HIV-specific IgA antibodies were rarely detected in the saliva of exposed uninfected infants (13). In SIV-infected rhesus monkeys, SIV-specific IgA antibodies isolated from milk had limited neutralization potency compared to that of IgG (45).…”

mentioning

confidence: 90%

HIV-Specific Functional Antibody Responses in Breast Milk Mirror Those in Plasma and Are Primarily Mediated by IgG Antibodies

Fouda

Yates

Pollara

et al. 2011

J Virol

139

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Despite months of mucosal virus exposure, the majority of breastfed infants born to HIV-infected mothers do not become infected, raising the possibility that immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies are present in the milk of HIV-infected mothers, but little is known about their virus-specific functions. In this study, HIV Env-specific antibody binding, autologous and heterologous virus neutralization, and antibody-dependent cell cytotoxicity (ADCC) responses were measured in the milk and plasma of 41 HIV-infected lactating women. Although IgA is the predominant antibody isotype in milk, HIV Env-specific IgG responses were higher in magnitude than HIV Env-specific IgA responses in milk. The concentrations of anti-HIV gp120 IgG in milk and plasma were directly correlated (r ‫؍‬ 0.75; P < 0.0001), yet the response in milk was 2 logarithm units lower than in plasma. Similarly, heterologous virus neutralization (r ‫؍‬ 0.39; P ‫؍‬ 0.010) and ADCC activity (r ‫؍‬ 0.64; P < 0.0001) in milk were directly correlated with that in the systemic compartment but were 2 log units lower in magnitude. Autologous neutralization was rarely detected in milk. Milk heterologous virus neutralization titers correlated with HIV gp120 Env-binding IgG responses but not with IgA responses (r ‫؍‬ 0.71 and P < 0.0001, and r ‫؍‬ 0.17 and P ‫؍‬ 0.30). Moreover, IgGs purified from milk and plasma had equal neutralizing potencies against a tier 1 virus (r ‫؍‬ 0.65; P < 0.0001), whereas only 1 out of 35 tested non-IgG milk fractions had detectable neutralization. These results suggest that plasma-derived IgG antibodies mediate the majority of the low-level HIV neutralization and ADCC activity in breast milk.

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“…HIV-specific IgA responses have also been documented in the absence of infection following oral exposure to HIV-1 through unprotected oral sex [49,50] and breast feeding [51]. Although there have been cohorts where no HIV-specific IgA has been evidenced [52], most HESN cohorts with documented mucosal exposure have evidenced detectable levels of HIV-specific IgA (see Table 2) [42,43].…”

Section: Humoral Responses To Hiv-1 In Hesn Subjectsmentioning

confidence: 99%

Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN)

Tomescu

Abdulhaqq

Montaner

2011

Clinical and Experimental Immunology

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SummaryThe description of highly exposed individuals who remain seronegative (HESN) despite repeated exposure to human immunodeficiency virus (HIV)-1 has heightened interest in identifying potential mechanisms of HIV-1 resistance. HIV-specific humoral and T cell-mediated responses have been identified routinely in HESN subjects, although it remains unknown if these responses are a definitive cause of protection or merely a marker for exposure. Approximately half of HESN lack any detectible HIV-specific adaptive immune responses, suggesting that other mechanisms of protection from HIV-1 infection also probably exist. In support of the innate immune response as a mechanism of resistance, increased natural killer (NK) cell activity has been correlated with protection from infection in several highrisk cohorts of HESN subjects, including intravenous drug users, HIV-1 discordant couples and perinatally exposed infants. Inheritance of protective NK KIR3DL1 high and KIR3DS1 receptor alleles have also been observed to be over-represented in a high-risk cohort of HESN intravenous drug users and HESN partners of HIV-1-infected subjects. Other intrinsic mechanisms of innate immune protection correlated with resistance in HESN subjects include heightened dendritic cell responses and increased secretion of antiviral factors such as b-chemokines, small anti-viral factors and defensins. This review will highlight the most current evidence in HESN subjects supporting the role of epithelial microenvironment and the innate immune system in sustaining resistance against HIV-1 infection. We will argue that as a front-line defence the innate immune response determines the threshold of infectivity that HIV-1 must overcome to establish a productive infection.

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Salivary human immunodeficiency virus (HIV)-1-specific immunoglobulin A in HIV-1-exposed infants in Kenya

Cited by 20 publications

References 32 publications

Vaccine Delivery to the Oral Cavity Using Coated Microneedles Induces Systemic and Mucosal Immunity

Vaccine Delivery to the Oral Cavity Using Coated Microneedles Induces Systemic and Mucosal Immunity

HIV-Specific Functional Antibody Responses in Breast Milk Mirror Those in Plasma and Are Primarily Mediated by IgG Antibodies

Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN)

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