Abstract Recent WHO vaccination guidance no longer recommends COVID-19 vaccination beyond the first booster in low risk population, citing high population-level hybrid immunity due to widespread omicron infections. 1 Although SARS-CoV-2 infection confers durable protection against reinfection, 2-4 it may also produce immune imprinting, which skews subsequent immune response to variant antigens toward the first-exposed antigen based on the antigenic distance. 5,6 China has the earliest and exclusively Wuhan-Hu-1(WH1)-imprinted population before the 2022 nation-wide omicron outbreak, 7 which offers a unique opportunity to study long-term immune imprinting between most antigenically distant strains. Here, we assessed pseudovirus neutralization activity and anti-WH1 receptor binding domain (RBD) antibodies in 4 Chinese cohorts with hybrid or vaccine-only imprinting, or naïve to SARS-CoV-2 prior to omicron BF.7 infection. Both hybrid and vaccine-only imprinting augmented post-infection serum neutralization of WH1 and omicron sub-variants BF.7/BQ.1.1/XBB.1.5 comparing to naïve background. Feedback from pre-existing high-affinity antibodies limited the magnitude of humoral immune response to omicron infection without compromising protection, while antigenic seniority of pre-existing cross-reactive B cells only slightly reduces forward neutralization breadth in hybrid- and RBD vaccine-imprinted participants. Our results support the effectiveness of hybrid immunity against omicron reinfection in long-term imprinted population and provide immunological basis for similar epidemiological findings. 8-10 

https://www.researchsquare.com/article/rs-3024491/latest.pdf

Humoral immune response to omicron infection in long-term Wuhan-Hu-1-imprinted population

Several vaccines have been found effective against COVID-19, usually administered in homologous regimens, with the same vaccine used for the prime and boost doses. However, recent studies have demonstrated improved protection via heterologous mix-and-match COVID-19 vaccine combinations, and a direct comparison among these regimens is needed to identify the best employment strategies. Here, we show a single-cohort comparison of changes to the humoral and cellular immune compartments following five different COVID-19 vaccines spanning three technologies (adenoviral, mRNA and inactivated vaccines). These vaccines were administered in a combinatorial fashion, resulting in sixteen different homologous and heterologous regimens. SARS-CoV-2-targeting antibody titres were highest when the boost dose consisted of mRNA-1273, independent of the vaccine used for priming. Priming with BBIBP-CorV induced less class-switching among spike-binding memory B cells and the highest antigen-specific T cell responses in heterologous combinations. These were generally more immunogenic in terms of specific antibodies and cellular responses compared to homologous regimens. Finally, single-cell analysis of 754 samples revealed specific B and T cell signatures of the vaccination regimens, indicating distinctive differences in the immune responses. These data provide new insights on the immunological effects of COVID-19 vaccine combinations and a framework for the design of improved vaccination strategies for other pathogens and cancer.

Distinct immune signatures discriminate SARS-CoV-2 vaccine combinations

Abstract The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer. 

/pdf/high-dimensional-analysis-of-16-sars-cov-2-vaccine-13a7ulxy.pdf

High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity

http://www.cell.com/article/S2666634022002197/pdf

Association of neutralizing breadth against SARS-CoV-2 with inoculation orders of heterologous prime-boost vaccines

The aim of the present study was to develop an immunochromatographic test (ICT) for the diagnosis of African trypanosomosis by using recombinant ribosomal P0 protein. The P0 C-terminal domain is highly antigenic and considered to be a major target of the antibody response in infected animals. Entire gene encoding the P0 protein was cloned, and expressed in Escherichia coli as a histidine-tagged recombinant protein (rP0). The rP0 was further purified by using nickel affinity chromatography under denaturing conditions. The rP0 was employed as a capture antigen in order to detect anti-P0 antibody in infected animal sera. Antigen-antibody reaction was detected by either colloidal-gold conjugated protein A or G. The results showed that colloidal gold-conjugated protein A and G were suitable for buffalo and cattle serum samples respectively. The rP0-ICT can detect specific antibody in 12,800-fold dilution serum. All sera from cattle or mouse infected with other protozoan parasites, such as Toxoplasma and Babesia, showed negative results. Field samples (150 serum samples from Uganda) were examined by rP0-ICT and rP0-ELISA showed that the positive rate is 48% (72/150) and 50% (75/150), respectively. The high agreement indicated that the rP0-ICT is reliable. This suggests that the rP0-based ICT can be used as a rapid on-site diagnostic method of salivarian trypanosomosis.

Preliminary studies for development of an immunochromatographic test (ICT) for detection of antibody against salivarian trypanosomes by using recombinant ribosomal P0 protein

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Association of neutralizing breadth against SARS-CoV-2 with inoculation orders of heterologous prime-boost vaccines

Preliminary studies for development of an immunochromatographic test (ICT) for detection of antibody against salivarian trypanosomes by using recombinant ribosomal P0 protein