Effect of Helminth Infection on SARS-CoV-2 Vaccine Efficacy: Study Findings and Conclusions

2024-01-18 02:56:46

In a recent study published in bioRxiv preprint server*, researchers tested the effect of helminth infection on the efficacy of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (mRNA) vaccine.

Helminths infect more than 25% of the world’s population. Hookworms, whipworms, and roundworms are responsible for most human helminth infections. Healthy people usually present with an asymptomatic helminth infection, with adult worms persisting in the gastrointestinal (GI) tract for years.

However, in immunocompromised individuals and children, a gastrointestinal infection can cause significant morbidity. Helminth infections have a negative effect on immune responses to vaccines against tuberculosis, hepatitis B, influenza and measles. However, the effect of infection on SARS-CoV-2 vaccine efficacy remains unknown.

Study: Intestinal infection impairs vaccine-induced T-cell responses and protection against SARS-CoV-2. Image credit: olgaru79 / Shutterstock

*important message: bioRxiv Publishes preliminary scientific reports that are not peer-reviewed, and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be considered as established information.

The research and findings

In the current study, the researchers evaluated the effect of anti-helminth infection on the effectiveness of the vaccine against the 2019 coronavirus disease (COVID-19) in mice. C57BL/6J mice were treated with mRNA encoding the SARS-CoV-2 Wuhan-1 spike; Animals were boosted three weeks later. Heligmosomoides Polygyros bakery (Hpb) inoculated twice, 12 days pre-prime and 12 days pre-fortification (P/B).

Two other groups were infected with Hpb, pre-prime (P) or pre-boost (B). Enzyme-linked immunosorbent assay (ELISA) revealed that vaccinated uninfected animals elicited immunoglobulin G (IgG) antibodies specific to the viral spike and its receptor domain (RBD) on day 15 after the first dose, which was enhanced on day. Count 15 after a second.

The infected groups (P, B and P/B) also had similar antibody responses; However, animals in the B group had significantly reduced IgG to spike and RBD, and those in the P/B group had a reduced response to RBD compared to uninfected immunized mice. Furthermore, there were no differences in spike-specific B-cell responses in infected and uninfected animals.

Regardless of infection status, all vaccinated animals induced similar neutralizing antibody (nAb) titers against SARS-CoV-2 WA1/2020 D614G. However, sera from all vaccinated groups had little or no inhibitory activity against Omicron BA.1 or BA.5. Besides, spike-specific clusters of differentiation 8 positive (CD8+) T cells were detectable in the spleen at day 15 after boost.

Interferon (IFN)γ+ and tumor necrosis factor (TNF)α+ CD8+ T cell responses were markedly reduced in Hpb-immunized mice. These animals also had reduced numbers of IFNγ+ TNFα–IFN+ interleukin 2 (IL-2+), and IFNγ+ TNFα+ CD8+ T cells, indicating that Hpb infection suppressed CD8+ effector T cell responses. Infection also suppressed the IFNγ+ TNFα+ CD4+ T cell responses.

Furthermore, infection of the lamina is biased toward T-helper 2 (Tχ2) differentiation, and this response was unaffected by vaccination. Next, the team looked at responses to Janssen’s adenoviral-vectored Ad26.COV2.S vaccine. Mice received the vaccine 12 and 30 days after Hpb infection. The number of spike-specific CD8+ T cells decreased two-fold 10 days after the boost.

Furthermore, the numbers and percentages of IFNγ+ TNFα+IFNγ+ IL-2+ and IFNγ+ TNFα– CD8+ T cells were reduced in Hpb-infected immunized mice compared to uninfected immunized animals. Infection also depleted IFNγ+ TNFα+ CD4+ T cells in immunized mice. Overall, Hpb infection impaired Ad26.COV2.S+ induced CD4 and CD8+ responses but to a lesser extent than with mRNA vaccination.

Moreover, K18-hACE2 mice were infected with Hpb and then immunized with two doses of mRNA vaccine. Naïve mice and unvaccinated mice infected with Hpb were controls. Animals were challenged with WA1/2020 D614G or Omicron BA.5.5 four to five weeks after the second vaccine dose. D614G infection of control animals reduced their body weight four to five days after infection. However, regardless of infection, all vaccinated mice were protected from weight loss.

Vaccinated mice infected with Hpb showed a decrease in viral burden, indicating that Hpb infection did not affect protection against D614G. In contrast, all vaccinated groups had a low nAb titer against BA.5.5. Vaccinated animals infected with Hpb lost about 15% of their weight. Furthermore, Hpb-infected immunized mice exhibited increased viral RNA and lung infectious virus compared to uninfected immunized mice.

Additional experiments revealed that Hpb infection resulted in defective vaccine-induced CD8+ T cell responses. Next, the researchers assessed whether signal transducer and activator of transcription 6 (STAT6) mediated defective Hpb CD8+ T cell responses. To this end, vaccination and helminth infection were repeated in wild-type inbred and stt6-/- Mice. mRNA immunization elicited equivalent CD8+ T cell responses in WT and uninfected stt6-/-.

Effector cytokine response and CD8+ T cell responses were similarly reduced in WT and infected WT stt6-/- Mice. This indicated suppression of CD8 associated helminth+ T cell response to mRNA vaccination was independent of STAT6 signaling. As such, the researchers explored alternative mechanisms and found helminth-induced IL-10 to be the likely suppressor, as blocking IL-10 in Hpb-infected animals restored the vaccine-induced T-cell response.

conclusions

In conclusion, the study assessed the effect of helminth infection on immune responses against COVID-19. The findings indicate that helminth infection did not significantly affect immunostimulating antibodies; However, infection affected T-cell responses. This impaired T-cell response was independent of whether mice were infected before the first or second dose.

In addition, Hpb infection impaired protection against Omicron BA.5.5 without significantly impairing protection against strain D614G. Together, the findings illustrate the deleterious effect of intestinal helminth infection on vaccine-induced T cell responses, and the impairment was likely through an IL-10-dependent pathway. Therefore, helminths should be considered as essential agents that can alter the efficacy and immunogenicity of the COVID-19 vaccine.

*important message: bioRxiv Publishes preliminary scientific reports that are not peer-reviewed, and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be considered as established information.