Do Adenovirus-Based COVID-19 Vaccines Increase the Risk of HIV Infection?

Coronavirus disease, also known as COVID-19 is an infectious disease caused by the newly discovered strain of Coronavirus (SARS-COV-2) which has resulted in a global pandemic.

Vaccines

Vaccines

Different Types of Vaccines

Different vaccines are being developed to counteract COVID- 19; these vaccines are in different stages of trial for their efficacy and safety. Pfizer vaccine is in the distribution phase after getting greenlit. US Biotech firm’s Moderna vaccine is awaiting approval for distribution following trials. Along with these, other vaccines are also being developed which are in different stages of trials. In trials safety of vaccines is checked, recently few reports have surfaced, which state the use of certain COVID-19 vaccines may increase the risk of HIV. Here we discuss the truth behind it.

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Australian Vaccine Canceled

Australia recently canceled a trial of an Australian vaccine developed by The University of Queensland after volunteers participating in its trial showed a false-positive result for HIV, raising concerns about the use and safety of other vaccines as well.

The protein-based vaccine showed two fragments of protein found in HIV. The use of these proteins did not risk infecting the volunteers with a virus, however, it increased the production of antibodies recognized by HIV tests at higher levels than expected leading to false-positive HIV results.

Adenovirus-based vaccines Risks

Along with this protein-based vaccine, vaccines based on viral proteins have also been linked to the development of HIV- especially adenovirus-based vaccines.

According to research published in The Lancet, researchers have urged caution before using Adenovirus-based vaccines (Ad5) for use in COVID-19 immunization based on their research on HIV vaccine trials using Adenovirus-based vaccine conducted 10 years back.

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Based on findings shown a decade ago, the use of Adenovirus-based vaccine using Ad5 vector in COVID-19 could increase the risk of acquiring HIV infection among men receiving these vaccines.

HIV Virus

HIV Virus

The researchers urged caution based on phase 2b trials on STEP and Phambili, which they carried out to determine the efficacy of Ad5 based vectored vaccines in preventing HIV infection. Both studies showed an increased risk in vaccinated men to HIV with the use of adenovirus-based vaccines.

According to the study, the risk of development of HIV was considerably increased in heterosexual men receiving the vaccine. The risks however were limited to men, with women not showing increased risk to HIV infection.

Phase 2b trials on STEP, showed an increased risk of HIV in uncircumcised men and adenovirus seropositive males who had reported having unprotected anal sex with HIV positive partner

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A thing to note about the study was that both STEP and Phambili vaccines did not contain an HIV envelope. Another similar study that used DNA prime and Ad5 vector having HIV envelope showed no increase in HIV infection rate in men.

The exact cause for increased risk of HIV in the use of Adeno virus-based vaccine is still unknown; however different studies have tried to explain the potential cause

Follow-up studies on Adenovirus based Ad5 vaccines

“The vaccine was highly immunogenic in the induction of HIV-specific CD4 and CD8 T cells; however, there was no difference in the frequency of T-cell responses after vaccination in men who did and did not later become infected with HIV in the STEP Study,” they wrote. “These findings suggest that immune responses induced by the HIV-specific vaccine were not the mechanism of increased acquisition. Participants with high frequencies of preimmunization Ad5-specific T cells were associated with a decreased magnitude of HIV-specific CD4 responses and recipients of the vaccine had a decreased breadth of HIV-specific CD8 responses, suggesting that pre-existing Ad5 immunity might dampen desired vaccine-induced responses.”

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Other studies have shown that the vaccine could act by enhancing HIV replication in Ad5 –specific CD4+ T cells. Although there is no evidence to link the increased risk of HIV in COVID-19 treatment using Ad5 vectored vaccines, the researchers involved have yet to give a concrete response to the concerns raised by this study.

However, experts have emphasized that the researchers have already considered the issues raised in the STEP trial including the very low chance of people who have previously come into contact with the viral vectors used for COVID-19 vaccines.

There are concerns around specifically the use of Ad5 vectored vaccines and the risks and uncertainties surrounding it. These should be cleared out and discussed with the participants of the trials. Oxford developed the AstraZeneca vaccine and Johnson and Johnson-based COVID vaccines use Ad26 viral vectors showing that the developers might have thoroughly applied the lessons learned from the STEP trial. Very few people have been exposed to this strain of the virus- so it is very unlikely that even people living in HIV endemic areas would be at a higher risk of developing HIV on receiving these Ad26 vectored vaccines.

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Precautions are being taken

China-based CanSino Biologics is developing Ad5 vectored vaccines for COVID-19 and it has acknowledged the potential risk of increased susceptibility to HIV on use of an Ad5 based adenovirus vaccine in a paper published in Lancet by CanSino in May this year.

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The researchers of the company have planned to monitor the participants of the trial in phase 2 and phase 3 of the study to assess if any increased risk of HIV acquisition occurs in them.

An important aspect that might need to be considered is that if the CD4+ T cell responses to adenoviruses are cross-reactive and recognize multiple strains of adenoviruses. Therefore a pre-existing CD4+ T cell response induced by a natural Ad5 infection might be boosted by a different adenovirus vector-like Ad26 as used in AstraZeneca and Johnson and Johnson developed COVID-19 vaccine.

Thus it might be necessary for these vaccines to make plans and conduct similar safety trials in their participants as done by CanSino.

As the vaccines for COVID-19 are planned to be distributed worldwide, it is necessary to clear all safety concerns surrounding these vaccines however minor they might seem.

People should recognize that not all COVID-19 vaccines put them at risk for HIV infections. Questions have been raised about vaccines using Adenovirus vectors. The questions put forward about these vaccines are not concrete evidence and the companies producing these vaccines will go through thorough checks before making them available for the public. So this implicated potential risk should not put off people from procuring the COVID-19 vaccines once they become available.

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References

Use of adenovirus type-5 vectored vaccines: a cautionary tale

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