Immune T-cell responses which are triggered following COVID-19 vaccination are affected by the type of vaccine administered reported a team of researchers led by Professor Antonio Bertoletti from Duke-NUS’ Emerging Infectious Diseases (EID) Programme in Cell Reports Medicine on 5 October. The team also found evidence of nasal-based immunity in vaccinated individuals who have been infected by the SARS-CoV-2 virus in an earlier study published in the Journal of Experimental Medicine on 16 August.   

In a third study, published in Nature Microbiology on 4 October, another Duke-NUS team in collaboration with the National Centre for Infectious Diseases (NCID), found that the Omicron variant is better able to escape the immune system than other SARS-CoV-2 variants. This enables it to remain the dominant variant around the globe.

“We present data indicating that SARS-CoV-2 variants have emerged under immune selection pressure and are evolving differently from related sarbecoviruses circulating in animals with less or no immune selection,” said Professor Wang Linfa from Duke-NUS’ EID Programme, who is also Executive Director of Singapore’s Programme for Research in Epidemic Preparedness and Response (PREPARE). Sarbecoviruses is a group of coronaviruses that encompasses SARS-CoV-1, SARS-CoV-2 and multiple coronaviruses in bats and pangolins that have the potential to infect humans.

Professor Wang Linfa's team collaborated with scientists from around the globe to analyse immune responses against a variety of sarbecoviruses

Wang and Professor David Lye, who is the director of the Infectious Disease Research and Training Office at NCID were part of an international effort of scientists in Singapore, Thailand, South Africa, Germany and the UK, to analyse immune responses against a variety of sarbecoviruses. 

They also found that people who had received the Pfizer BioNTech mRNA vaccine and were subsequently infected with the virus displayed broader immune responses compared with those who had received the vaccine but had not been infected.

In a similar vein, Bertoletti’s team detected long-lasting immune T cells targeting the SARS-CoV-2 virus in the noses of people who were infected following vaccination with the Pfizer-BioNTech mRNA vaccine. The same T cells were not present in the nasal cavities of individuals who had only received the vaccine.

“We also found that the T cells in the vaccinated and then infected group persisted for at least 20 weeks and were able to recognise various SARS-CoV-2 proteins, including the non-spike proteins that are more conserved between the different viral variants,” said Ms Joey Lim Ming Er, first author of the study and a PhD student in Bertoletti’s lab at Duke-NUS. “This is important because it means that these T cells would likely be capable of recognising cells infected with the Omicron variant of SARS-CoV-2 despite its extensive spike protein mutations.”

Professor Antonio Bertoletti and his team have been studying the T-cell responses after COVID-19 infection and vaccination

 
Building on their work characterising immune responses in vaccinated individuals, the team next looked at T-cell responses in individuals who received inactivated SARS-CoV-2 and spike mRNA vaccines. They found that inactivated vaccines, which expose the immune system to the entire non-viable virus, elicited a broad immune response against proteins on the virus including the spike protein, as well as the membrane and nucleoprotein that have fewer mutations in Omicron.

“This combination of membrane, nucleoprotein and spike-specific T-cell response is quantitatively comparable to the sole spike T-cell response induced by the mRNA vaccine. It also effectively tolerates the mutations characterising the Omicron lineage,” said Lim.

Unlike the mRNA vaccines, the inactivated virus vaccines did not seem to trigger cytotoxic CD8 T cells known for their ability to kill and clear cells that have been infected by a virus. Instead, they stimulated another type of T cells—CD4 T helper cells, which activate other immune cells to respond to an infection when they encounter a viral antigen.

“Since inactivated SARS-CoV-2 vaccines can generate T cell responses towards other viral proteins, this more heterogenous response could be beneficial, in comparison to the current spike targeting strategy of other vaccines.

Professor Antonio Bertoletti

“Since inactivated SARS-CoV-2 vaccines can generate T cell responses towards other viral proteins, this more heterogenous response could be beneficial, in comparison to the current spike targeting strategy of other vaccines. However, larger studies are needed to clarify the impact of these T-cell responses in SARS-CoV-2 disease progression to better design vaccines for controlling severe COVID-19 after infection by Omicron or future variants,” concluded Bertoletti.