In contrast to the mRNA vaccines, Ad26.COV2.S (Janssen COVID-19 vaccine) is single-shot replication-incompetent adenovirus-type-26 vectored vaccine encoding a stabilized variant of the SARS-CoV-2 S protein.1 Adenovirus vaccines have been widely used,2 efficiently infect host cells, and may be expected to elicit stronger Th1-biased cellular immunity than mRNA vaccines, which contributes to B-cell differentiation and antibody production.3 For transplant recipients, given limited immunogenicity of mRNA vaccines,4 the Janssen vaccine platform might be a better choice. We sought to quantify the antispike antibody response to Janssen COVID-19 vaccination in transplant recipients and compare it to recipients of the mRNA series.
We leveraged our prospective cohort of transplant recipients without prior COVID-19 who underwent SARS-CoV-2 vaccination between December 16, 2020, and March 27, 2021.5 Serologic testing was undertaken on the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (range <0.4 to >250 U/mL [positive ≥0.8 U/mL]), which tests for antibodies against the receptor-binding domain (RBD) of the spike protein at 1 mo after COVID-19 vaccine (Janssen or mRNA).
We compared the percentage of participants with detectable anti-RBD antibody in the Janssen group (n = 12) to the mRNA group (n = 725) using Fisher’s exact test (Table S1, SDC, https://links.lww.com/TP/C249). We compared the 2 platforms using logistic regression adjusting for age (excluding those >70 in the mRNA group to match the Janssen group), sex, race, years since transplant (excluding those >20 y since transplant in the mRNA group to match the Janssen group) and immunosuppression. Two sensitivity analyses were undertaken weighting-by-the-odds, first weighting on age and years since transplant, and second weighting on antimetabolite immunosuppression and years since transplant. We then used the Wilcoxon rank-sum test to compare nonnegative anti-RBD titers of the Janssen group to those of the mRNA group (n = 430). This study was approved by the Johns Hopkins institutional review board.
We studied 12 transplant recipients who underwent Janssen vaccine (Table S2, SDC, https://links.lww.com/TP/C249). At a median (IQRs) 33 d (31–44) after vaccination, anti-RBD antibody was detectable in only 2 of 12 participants who received the Janssen vaccine compared with 430 of 725 who completed the mRNA vaccine series (17% versus 59%, P = 0.005). Those who received the Janssen vaccine had lower odds (aOR 0.11; 95% CI, 0.02-0.53; P = 0.006) of developing anti-RBD antibodies than those who completed the mRNA series. This association was similar in sensitivity analyses weighting by age and years since transplant (aOR 0.13; 95% CI, 0.03-0.61; P = 0.01) and immunosuppression and years since transplant (aOR 0.17; 95% CI, 0.04-0.76; P = 0.02). Median anti-RBD Ig titers in the Janssen group were significantly lower than the mRNA group (2.39 versus 106.9 U/mL) (P = 0.047) (Figure 1).
In this case series of humoral response to the Janssen vaccine, only 2 of 12 participants mounted a detectable anti-RBD antibody response, which was significantly lower than what was seen among recipients of the mRNA vaccine series. Additionally, titers were significantly lower than those in the mRNA group.
These early results suggest that Janssen vaccine may result in even lower humoral immunity than mRNA vaccines in immunosuppressed transplant patients. The generalizability of these findings to other immunosuppressed populations merits further investigation.
1. Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1–2a trial of Ad26.COV2.S Covid-19 vaccine. N Engl J Med. 2021;384:1824–1835.
2. Custers J, Kim D, Leyssen M, et al.; Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG). Vaccines based on replication incompetent Ad26 viral vectors: standardized template with key considerations for a risk/benefit assessment. Vaccine. 2021;39:3081–3101.
3. Stephenson KE, Le Gars M, Sadoff J, et al. Immunogenicity of the Ad26.COV2.S vaccine for COVID-19. JAMA. 2021;325:1535–1544.
4. Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204–2206.
5. Boyarsky BJ, Werbel WA, Avery RK, et al. Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021;325:1784–1786.