Humoral and cellular immunogenicity of homologous and heterologous booster vaccination in Ad26.COV2.S-primed individuals: Comparison by breakthrough infection

Abstract

BackgroundWhether or not a single-dose Ad26.COV2.S prime and boost vaccination induces sufficient immunity is unclear. Concerns about the increased risk of breakthrough infections in the Ad26.COV2.S-primed population have also been raised.MethodsA prospective cohort study was conducted. Participants included healthy adults who were Ad26.COV2.S primed and scheduled to receive a booster vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. The IgG anti-receptor binding domain (RBD) antibody titers, neutralizing antibody (NAb) titers (against wild type [WT] and Omicron [BA.1 and BA.5]), and Spike-specific interferon-γ responses of the participants were estimated at baseline, 3–4 weeks, 3 months, and 6 months after booster vaccination.ResultsA total of 89 participants were recruited (26 boosted with BNT162b2, 57 with mRNA-1273, and 7 with Ad26.COV2.S). The IgG anti-RBD antibody titers of all participants were significantly higher at 6 months post-vaccination than at baseline. The NAb titers against WT at 3 months post-vaccination were 359, 258, and 166 in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. Compared with those against WT, the NAb titers against BA.1/BA.5 were lower by 23.9/10.9-, 16.6/7.4-, and 13.8/7.2-fold in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively, at 3 months post-vaccination. Notably, the NAb titers against BA.1 were not boosted after Ad26.COV2.S vaccination. Breakthrough infections occurred in 53.8%, 62.5%, and 42.9% of the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. No significant difference in humoral and cellular immunity was found between individuals with and without SARS-CoV-2 breakthrough infections.ConclusionBooster vaccination elicited acceptable humoral and cellular immune responses in Ad26.COV2.S-primed individuals. However, the neutralizing activities against Omicron subvariants were negligible, and breakthrough infection rates were remarkably high at 3 months post-booster vaccination, irrespective of the vaccine type. A booster dose of a vaccine containing the Omicron variant antigen would be required.

Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan

“…Among the 14 individuals who received heterologous vaccines, 13 successfully acquired cellular immunity. This finding supports the effectiveness of the heterologous vaccine administration strategy ( 34 – 36 ). These results provide valuable data for considering future vaccination strategies for vulnerable populations.…”

Effect of SARS-CoV-2 Breakthrough Infection on HIV Reservoirs and T-Cell Immune Recovery in 3-Dose Vaccinated People Living with HIV

“…Previous studies have suggested that a rapid and extensive recall of T cells occurs after breakthrough infection, which benefits virological control [33]. Data regarding the differences in T-cell responses after breakthrough infection between the homologous and heterologous booster groups are still controversial [34,35]. Data from our study demonstrated that the heterologous vaccine regime induced a significant increase in CD4 + T-cell activation compared to that in homologous booster individuals.…”

Aerosol Inhalation of Chimpanzee Adenovirus Vectors (ChAd68) Expressing Ancestral or Omicron BA.1 Stabilized Pre–Fusion Spike Glycoproteins Protects Non–Human Primates against SARS-CoV-2 Infection

“…The two monovalent and the bivalent vaccines elicited substantial cross–neutralizing antibody responses against Omicron BA.4/5 variants. Indeed, homologous booster with vector–based vaccines expressing the same antigen is less effective than heterologous booster with the same vector–based vaccines expressing different immunogens [ 60 ]. The heterologous immunization approach is thus a potentially efficacious approach to controlling infection from the Delta strain, the Omicron sublineages, and the hybrid “Deltacron” variant [ 60 ].…”