Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients

Abstract

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 (P < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group (P < 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines.

Keywords: cancer immunotherapy; cancer vaccine; chimpanzee adenovirus serotype-68; human adenovirus serotype-5; neutralizing antibodies.

Figure 1

Distribution of neutralizing antibody (NAb) titers against AdHu5 and AdC68 in positive samples. NAb titers were stratified in the following tiers: low titer (≥20 and ≤160), medium titer (≥320 and ≤640), and high titer (≥1,280). Across positive samples from all of the human subjects, the NAb titers against AdHu5 from low to high were 51.02, 33.79, and 15.19%, respectively. The AdC68 NAb titers in positive samples from low to high were 96.67, 3.33, and 0%, respectively, which was significantly different from AdHu5 (P < 0.01). For positive samples from the cancer subjects, the NAb titers against AdHu5 from low to high were 51.02, 33.79, and 15.19%, respectively. However, most cancer subjects exhibited low NAb titers against AdC68 (≥20 and ≤160, 95.83%), and a small fraction of cancer subjects exhibited a medium level of AdC68 NAb titers (≥320 and ≤640, 4.17%). For the healthy adult volunteers, the AdHu5 NAb titers in the positive samples from low to high were 32.19, 35.62, and 32.19%, respectively, whereas all of titers from the positive NAb samples against AdC68 were lower or equal to 160.

Figure 2

Distribution of AdHu5 and AdC68 neutralizing antibody (NAb) titers in positive samples from cancer patients in different clinical stages. NAb titers were stratified in the following tiers: low titer (≥20 and ≤160), medium titer (≥320 and ≤640), and high titer (≥1,280). For stage-I positive subjects, the AdHu5 NAb titers from low to high were 58.54, 34.15, and 7.32%, respectively, whereas the AdC68 NAb titers from low to high were 94.55, 5.45, and 0%, respectively; a significant difference existed between the AdHu5 NAb and AdC68 NAb titers among stage-I positive subjects (P < 0.01). For stage-II positive subjects, the AdHu5 NAb titers from low to high were 64.81, 29.63, and 5.56%, respectively, while all of the positive AdC68 NAb sample titers were lower or equal to 160. For stage-III positive subjects, the AdHu5 NAb titers from low to high were 61.45, 32.53, and 6.02%, respectively. However, most cancer patients exhibited low NAb titers against AdC68 (≥20 and ≤160, 94.12%), and a small fraction of cancer patients exhibited a medium level of AdC68 NAb titers (≥320 and ≤640, 5.88%). For stage-IV positive subjects, the AdHu5 NAb titers from low to high were 40.91, 45.45, and 13.64%, respectively, while the AdC68 NAb titers from low to high were 86.67, 13.33, and 0%, respectively; this was significantly different from AdHu5 (P < 0.05).

Figure 3

Distribution of AdHu5 and AdC68 neutralizing antibody (NAb) titers in positive samples from lung squamous cell carcinoma and adenocarcinoma subjects. NAb titers were stratified in the following tiers: low titer (≥20 and ≤160), medium titer (≥320 and ≤640), and high titer (≥1,280). For the positive samples from lung squamous cell carcinoma patients, the AdHu5 NAb titers from low to high were 48.28, 37.93, and 13.79%, respectively, while the AdC68 NAb titers from low to high were 92.86, 7.14, and 0%, respectively; this was significantly different from AdHu5 (P < 0.05). For positive samples from lung adenocarcinoma patients, the AdHu5 NAb titers from low to high were 74.19, 22.58, and 3.23%, respectively, while all of the positive AdC68 NAb sample titers were lower or equal to 160. However, no significant difference in the distribution of the two vectors in lung adenocarcinoma patients was observed (P > 0.05).