Heterologous Ad.26.COV2.S versus homologous BNT162b2/mRNA-1273 as a third dose in solid organ transplant recipients seronegative after two-dose mRNA vaccination

Abstract

Heterologous vaccination (“mixing platforms”) for the third (D3) dose of SARS‐CoV‐2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA‐1273; D3‐mRNA) versus heterologous (Ad.26.COV2.S; D3‐JJ) D3 among 377 SARS‐CoV‐2‐infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti‐spike titers and used weighted Poisson regression to evaluate seroconversion and development of high‐titers, comparing D3‐JJ to D3‐mRNA, at 1‐, 3‐, and 6 month post‐D3. 1‐month post‐D3, seroconversion (63% vs. 52%, p = .3) and development of high‐titers (29% vs. 25%, p = .7) were comparable between D3‐JJ and D3‐mRNA recipients. 3 month post‐D3, D3‐JJ recipients were 1.4‐fold more likely to seroconvert (80% vs. 57%, weighted incidence‐rate‐ratio: wIRR = 1.10 1.40 1.77 , p = .006) but not more likely to develop high‐titers (27% vs. 22%, wIRR = 0.44 0.92 1.93 , p = .8). 6 month post‐D3, D3‐JJ recipients were 1.41‐fold more likely to seroconvert (88% vs. 59%, wIRR = 1.04 1.41 1.93 , p = .029) and 2.63‐fold more likely to develop high‐titers (59% vs. 21%, wIRR = 1.38 2.63 5.00 , p = .003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3.

Predicting a Positive Antibody Response After 2 SARS-CoV-2 mRNA Vaccines in Transplant Recipients: A Machine Learning Approach With External Validation

“…23 There is some encouraging evidence to support heterologous vaccination as a strategy to improve immune response rates among poor responders to the initial series, but further exploration of this strategy is needed. 24 With this novel approach to predicting antibody response to mRNA SARS-CoV-2 vaccination in SOTRs, MMF use, older age, and a shorter time since transplant were the strongest factors associated with failure to generate an antibody response. In an era where universal antibody testing among transplant recipients has not yet been adopted, this model provides guidance for risk-based antibody testing.…”

“…23 There is some encouraging evidence to support heterologous vaccination as a strategy to improve immune response rates among poor responders to the initial series, but further exploration of this strategy is needed. 24 …”

Immunogenicity of Ad26.COV2.S prime and two subsequent doses of mRNA SARS‐CoV‐2 vaccines in solid organ transplant recipients: A case series

“…Heterologous vaccination has been explored in small populations of solid organ transplant recipients (SOTRs), 1 , 2 , 3 , 4 yet 38% of participants had persistently suboptimal response indicating potential role for further vaccine doses. 1 The US CDC currently recommends immunocompromised adults who received an Ad26.COV2.S prime to receive one additional dose of SARS‐CoV‐2 mRNA vaccine, either BNT162b2 or mRNA‐1273, followed by two mRNA vaccine boosters, although the efficacy of this strategy in immunocompromised persons is not known.…”

“…Within our previously described observational cohort, 2 , 3 11 SOTRs reported an Ad26.COV2.S‐prime (D1) followed by two doses of BNT162b2 ( n = 5) or mRNA‐1273 ( n = 6). SOTRs who reported pre‐D1 SARS‐CoV‐2 infection were excluded.…”

“…

Heterologous vaccination has been explored in small populations of solid organ transplant recipients (SOTRs), [1][2][3][4] yet 38% of participants had persistently suboptimal response indicating potential role for further vaccine doses. 1 The US CDC currently recommends immunocompromised adults who received an Ad26.COV2.S prime to receive one additional dose of SARS-CoV-2 mRNA vaccine, either BNT162b2 or mRNA-1273, followed by two mRNA vaccine boosters, although the efficacy of this strategy in immunocompromised persons is not known.We evaluated serial antispike antibody responses and reactogenicity among SOTRs who received two doses of mRNA vaccine following Ad26.COV2.S prime.Within our previously described observational cohort, 2,3 11 SOTRs reported an Ad26.COV2.S-prime (D1) followed by two doses of BNT162b2 (n = 5) or mRNA-1273 (n = 6).

…”