COVID-19: Two doses of Oxford vaccine boost immune responses in pigs

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While a single dose induced antigen-specific antibody and T cells responses in pigs, the booster dose enhanced the antibody responses with a significant increase in neutralising antibody levels. There was no significant increase in antibody responses in mice after the booster dose.

A study in pigs has found that two doses of Oxford vaccine (ChAdOx1 nCoV-19) given as prime-boost produce greater antibody responses than a single dose. The researchers found that even a single dose was sufficient in inducing antigen-specific antibody and T cells responses in pigs, the booster dose elevated the antibody responses, with a significant increase in neutralising antibody levels. There was no significant increase in antibody responses in mice after the booster dose.

“Whilst a single dose induced antigen-specific antibody and T cells responses, booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres,” researchers write in a preprint posted on June 20 on bioRxiv preprint server. The preprint is yet to be peer-reviewed and published in a scientific journal.

The Pune-based Serum Institute announcing plans to manufacture the vaccine the moment the Phase-3 trial or the combined Phase-2/Phase-3 trial begins.

Earlier study on monkeys

An earlier study posted on bioRxiv preprint server by the researchers found that a single dose of the vaccine induced a humoral and cellular immune response in rhesus macaques. While the vaccinated rhesus macaques did not develop pneumonia, the vaccination was unable to prevent infection when exposed to the virus. They found that the vaccinated animals that were infected when exposed to the virus had “significantly reduced” viral load in bronchoalveolar lavage fluid and respiratory tract tissue compared with control animals.

Pigs, not mice, showed enhanced responses

The study evaluated a prime-boost vaccine regimen in both mice and pigs. While a single dose of the vaccine induced antigen-specific antibody and T cells responses in both mice and pigs, the booster dose enhanced the antibody responses significantly in just one mouse strain. But in the case of pigs, the booster dose significantly enhanced the antibody responses.

Pigs in the prime-only group received the vaccine on day zero, while the animals in the prime-booster group received the vaccine on day zero and day 28.

Booster dose elevates immune responses

Significant FL-S specific antibody titres were detected in both pig groups — prime-only and prime-boost groups. But the booster dose increased the antibody levels significantly in the animals in the prime-booster group. Similarly, in the case of the RBD-specific antibodies, significant levels were seen in both groups from 14 post vaccination. However, there was significant increase in the RBD-specific antibody level in animals belonging to the prime-boost group 35 days post vaccination. The RBD-specific antibody levels in the prime-boost group was greater than the prime-only animals 35 days post vaccination.

In the case of neutralising antibodies, they were detected in two-third of animals in both groups. However, animals that received the booster dose exhibited significantly greater levels of neutralising antibodies two weeks after the second dose compared with animals that received only one dose.

Similarly, at day 42, T cell responses were higher in pigs that received two doses of the vaccine compared with animals that received only one dose, thus demonstrating that the prime-boost regimen trended toward a higher response. In addition to T cell responses, pigs also exhibited robust Th1-like CD4+ and CD8+ T cell responses in pigs.

“This has important implications for COVID-19 vaccine development as virus-specific T cells are thought to play an important role in SARS-CoV-2 infection,” they write.

Phase 2-3 human clinical trials

On April 23, Phase-1 human clinical trial began on healthy volunteers aged 15 and 55. According to Oxford University website, more than 1,000 immunisations had been completed as on May 22 and follow-up was going on.

On May 22, the trial was all set to graduate to the next stage of Phase 2-3. The study will enroll up to 10,260 adults and children. The Phase-2 trial will enroll a small number of older adults (56-69 years and over 70 years) and children (between 5-12 years) to study how well the immune system responds in older people or children.

The Phase-3 will assess the efficacy of the vaccine in a large number of people over 18 years of age. The researchers will assess how well the vaccine helps “prevent people from becoming infected and unwell” with COVID-19.

In both Phase-2 and Phase-3, participants will be randomised to receive one or two doses of the Oxford vaccine or MenACWY vaccine that protects against four strains of meningococcal bacteria (control group).

Trials to begin in Brazil, South Africa

Due to reduced transmission rate in UK, University of Oxford has been looking at other countries where the virus spread is still high. Accordingly, the Oxford vaccine will now be tested in South Africa and Brazil.

In Brazil, the vaccine will be tested on 2,000 participants in Sao Paulo and 1,000 participants in Rio de Janeiro. In South Africa, the vaccine will be tested at several sites.

Published in The Hindu on June 24, 2020