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The Johnson & Johnson vaccine is more effective after natural infection

The Johnson & Johnson vaccine is an adenovirus vectored vaccine expressing the spike protein of the Wuhan ancestral strain. It has 85% efficacy against severe forms of the disease and is administered in a single dose. It is helpful for countries with difficulties accessing vaccines. However, while we know that a supplementary dose of an mRNA vaccine increases the efficacy of the immune response against variants of concern (VoC), this question has not been resolved for the Johnson & Johnson vaccine.

In order to provide answers, South African researchers (at the University of Cape Town) carried out a study. It should be noted that South Africa experienced a first wave of infections dominated by the D416G variant in summer 2020, followed by a second wave dominated by the Beta variant in November 2020. The scientific approach of the researchers involved the observation of healthcare workers vaccinated with the Johnson & Johnson vaccine, and divided into 3 groups:

  • 20 workers who had never been infected
  • 20 workers with prior infection by the D416G ancestral variant
  • 20 workers with prior infection by the Beta (South African) variant

Serological samples were taken from the participants.

 What were the main observations?

One month after vaccination, the 3 groups showed equivalent levels of anti-spike antibodies (neutralising and non-neutralising) that recognised both the D416G and Beta variants.

One month later, the 2 infected groups showed levels that were 3 times higher. The level of neutralising antibodies was relatively small in the non-infected group, while this figure increased 12- or 13-fold in the 2 infected groups. In the non-infected group, the antibodies of only 15% of participants were capable of neutralising Beta, with 22% able to neutralise Delta. Cross-neutralisation was much higher after infection. However, the group infected with D416G neutralised Beta and Delta less effectively than D416G, while the group infected with Beta was able to neutralise D416G and Beta in a similar way, but efficacy was reduced 6-fold against Delta.

The infected groups showed a better Fc effector response to the same degree against D416G, Beta and Delta (immune cells recognise antibodies by their non-pathogen-specific ‘tail’). Unlike the neutralising response, the Fc response showed effective cross-reactivity against the Beta and Delta VoC, irrespective of whether this was induced by a single vaccination or not.

After vaccination, the efficacy of the T cell response was high and comparable in the 3 groups (secretion of IFNɣ, TNF⍺ and IL2). However, the CD4 T cell response was higher in the non-infected group (5,7-fold change) , since a response was already present in the infected groups (1,5-fold change for the D416G group and 1,1-fold change for the Beta group). Production of CD8 T cells was significant and comparable in the 3 groups, but lower than the CD4 T response. The CD4 T response is maintained against the Beta and Delta variants in the 3 groups, while the CD8 T response falls by half against Delta in a third of patients.

The Johnson & Johnson vaccine, when given after prior natural infection, therefore enables an increase in the protective antibody response (neutralising and Fc effectors) and cross-reactivity against VoC. The vaccine induces an effective cellular and cross-reactive response even without prior infection. However, the range of protection depends on the strain involved in infection, since neutralisation falls against Delta if individuals were initially infected by D416G or Beta. This observation is important for vaccinal strategies in South Africa, where 20 – 40% of the population has SARS-CoV-2 seropositivity, as well as for the design of second-generation vaccines (that target VoC more effectively) in certain specific regions of the world.

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