SARS-CoV-2 immunity and vaccine strategies in people with HIV

Abstract

Current SARS-CoV-2 vaccines, based on the ancestral Wuhan strain, were developed rapidly to meet the needs of a devastating global pandemic. People living with HIV (PLWH) have been designated as a priority group for SARS-CoV-2 vaccination in most regions and varying primary courses (2 or 3-dose schedule) and additional boosters are recommended depending on current CD4+ T cell count and/or detectable HIV viraemia. From the current published data, licensed vaccines are safe for PLWH, and stimulate robust responses to vaccination in those well controlled on antiretroviral therapy and with high CD4+ T cell counts. Data on vaccine efficacy and immunogenicity remain, however, scarce in PLWH, especially in people with advanced disease. A greater concern is a potentially diminished immune response to the primary course and subsequent boosters, as well as an attenuated magnitude and durability of protective immune responses. A detailed understanding of the breadth and durability of humoral and T cell responses to vaccination, and the boosting effects of natural immunity to SARS-CoV-2, in more diverse populations of PLWH with a spectrum of HIV-related immunosuppression is therefore critical. This article summarises focused studies of humoral and cellular responses to SARS-CoV-2 infection in PLWH and provides a comprehensive review of the emerging literature on SARS-CoV-2 vaccine responses. Emphasis is placed on the potential effect of HIV-related factors and presence of co-morbidities modulating responses to SARS-CoV-2 vaccination, and the remaining challenges informing the optimal vaccination strategy to elicit enduring responses against existing and emerging variants in PLWH. Lay Abstract People living with Human Immunodeficiency Virus (PLWH), appear to be at a higher risk (approximately 15%) of becoming more seriously unwell if they are infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes COVID-19 disease, and at least twice as likely to die from COVID-19 as the rest of the population. SARS-CoV-2 vaccination and boosters are recommended for all PLWH. However, there is limited information about the protective immune responses to both vaccination (and actual infection), the protection against serious COVID-19 disease, and whether the safety profile of the vaccines, which are very safe in the general population, differs in PLWH. Here we summarise findings from studies which looked specifically at vaccine-related immune responses in PLWH, and discuss factors – such as age, known to impact negatively on immune responses in the general population, to see whether this effect is worse in PLWH. A better understanding of these issues will help guide tailored vaccination and prevention strategies for PLWH.

Fourth Dose of mRNA COVID-19 Vaccine Transiently Reactivates Spike-Specific Immunological Memory in People Living with HIV (PLWH)

“…The SARS-CoV-2 associated disease (COVID-19) can be developed in asymptomatic or mild forms, but may also cause severe dysregulation, leading to hospitalization and a poor outcome [ 31 ]. PLWH are a category of individuals whose immune dysfunction places them at risk of developing severe COVID-19 [ 22 ], and they represented a very small portion of the cohorts enrolled for the vaccines’ trials [ 13 ]. There are only a few studies reporting data on the vaccine-induced protection in this population [ 23 , 32 , 33 , 34 ].…”

“…Data on the COVID-19 vaccine efficacy and immunogenicity remain scarce in PLWH [ 22 ]. It has been shown that a third mRNA vaccine dose strongly boosts the humoral immune response in PLWH at higher levels, compared to the post-second dose, regardless of the CD4+ T cell count [ 23 ].…”

Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles

“…7 We and others have previously shown a failure to mount a robust antibody response following COVID-19 vaccination in advanced HIV infection with low CD4 T cell counts below 200 cells/µl. [8][9][10][11][12] Data on vaccine efficacy and immunogenicity in PLWH remains limited (reviewed in 13 ), and while there are some conflicting results, meta-analyses 14 and recent studies 15 have shown reduced levels of seroconversion and neutralization after a second dose of viral vector vaccine dose in PLWH receiving cART, with lower CD4 T cell count/viraemia and older age resulting in a more impaired response and more rapid breakthrough infection. 16 Assessment of vaccine efficacy has been continually complicated by the ongoing emergence of variants of concern (VOC), with the Alpha, Beta, Delta and Omicron variants being observed to progressively evade antibodies 17,18 raised against the original Wuhan-Hu-1 strain in most vaccines.…”

Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles

“…This suggests additional doses/targeted vaccines could be merited, especially given 28% of SARS-CoV-2 naïve PLWH failed to neutralize Omicron after the third vaccine dose. Previous studies among similar cohorts of PLWH with undetectable HIV viral loads have produced mixed results, as previously reviewed (Mullender et al, 2022). SARS-CoV-2 viral vector vaccines have shown similar magnitude and durability of antibody responses to HIV-negative controls (Frater et al, 2021; Ogbe et al, 2022b) but reduced levels of seroconversion and neutralization have been reported after two doses in PLWH in a more recent study (Woldemeskel et al, 2022).…”

“…Data on vaccine efficacy and immunogenicity in PLWH remains limited (reviewed in (Mullender et al, 2022)), and while there are some conflicting results, meta-analyses (Tamuzi et al, 2022) and recent studies (Woldemeskel et al, 2022) have shown reduced levels of seroconversion and neutralization after a second dose of viral vector vaccine dose in PLWH, with lower CD4 T cell count/viraemia and older age resulting in a more impaired response and more rapid breakthrough infection (Sun et al, 2022). Data after three vaccine doses are scarce, especially of evaluating efficacy against Omicron.…”