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In this study we evaluated and compared the kinetics
In this study we evaluated and compared the kinetics and duration of the oral and systemic HPV-16 and HPV-18 specific antibody response to three doses of the qHPV vaccine in mid-adult aged HIV+ men from the AIDS Malignancy Cohort (AMC) 052 trial and mid-adult aged HIV− men from the Mid-Adult Male [MAM] trial. Additionally, antibody avidity was determined. This is the first study evaluating longevity of the mucosal antibody responses, and serum HPV antibody avidity following HPV vaccination in HIV+ males when compared to healthy subjects. With this work we aim to develop better understanding of the local and systemic HPV- specific antibody responses to the qHPV vaccine in an HIV-infected male mid-adult vaccinated cohort.
Materials and methods
Discussion
This is the first study to directly compare the immune response of HIV+ and HIV− mid-adult aged men following receipt of a 3-dose regimen of the qHPV vaccine. A high and comparable percentage of HIV+ and HIV− men sero-converted following receipt of three doses of vaccine. While peak serum antibody levels were lower among HIV+ compared with HIV− men, geometric mean plateau levels at Month 18 were comparable. As has been demonstrated in other trials, HIV+ individuals entering HPV-seropositive prior to receiving vaccine achieve considerably higher antibody levels at Month 7 compared to those who are HPV-seronegative at the time of vaccination. Interestingly, the higher antibody response in HPV-seropositive men was sustained among HIV+ men but not HIV− men through the 18-month time point.
Overall, HIV-infected individuals have higher rates of HPV infection, they are more likely to have multiple HPV types and persistent infections, and are at increased risk of oropharyngeal cancer and other HPV-associated cancers compared with HIV− individuals [22], [23], [24]. Recently, we published that the quadrivalent HPV vaccine induces HPV-specific A-1155463 synthesis in the oral cavity following HPV vaccination in mid adult, HIV− males, although at much lower levels than the ones found in serum [9]. However, the longevity and the concentration of antibodies at plateau levels, particularly at the oral cavity in HIV-infected individuals was unknown.
Serum HPV-16 and HPV-18 antibody geometric mean levels were >2-fold lower in HIV+ men at Month 7 but not significantly different at Month 18 compared with HIV− men. Significantly lower antibody levels were observed in individuals without viral suppression at Month 7, indicating the inverse association between plasma HIV-1 RNA and peak antibody responses. This association has been observed in other studies among HIV-infected individuals [25]. Lack of significance for other time points or for HPV-18 antibody measurements may be related to the small sample size of men with >200 copies/ml (n = 14). Larger sample sizes are required to appropriately evaluate this association. However, results from this study are in agreement with previous findings demonstrating a lower antibody response in HIV+ individuals, which was reported to be influenced by CD4 T cell depletion and higher HIV viral loads [11], [12], [14]. This is also consistent with immunogenicity findings from other vaccines administered in HIV+ individuals [26], [27].
Findings from this study indicate that oral anti-HPV-16 and anti-HPV-18 antibody levels at Month 18 are markedly reduced compared with the levels observed with peak responses, at Month 7 (1 month following administration of the three doses of vaccine), particularly for HPV-18 among HIV− men. HIV+ individuals showed markedly higher oral HPV antibody prevalence on Day 1 and Month 18, for both HPV-16 and HPV-18, but not at peak time of antibody responses, at Month 7. Only oral HPV-16 antibody levels at Month 7 were significantly lower in HIV+ compared with HIV− men, while antibody levels, for both HPV-16 and HPV-18, were comparable with a tendency for higher levels in HIV+ individuals once plateau levels were achieved.