Influenza vaccine in pregnant women with HIV: are we there?
Authors: Sharon Nachman
Journal: The Lancet HIV (2020)

In The Lancet HIV, Marta Nunes and colleagues report their clinical trial assessing three different approaches to influenza vaccination in pregnant women with HIV in South Africa.1Nunes MC Cutland CL Moultrie A et al.Immunogenicity and safety of different dosing schedules of trivalent inactivated influenza vaccine in pregnant women with HIV: a randomised controlled trial.Lancet HIV. 2020; (published online Jan 3)https://doi.org/10.1016/S2352-3018(19)30322-4Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar Recognising that the standard vaccine, while licensed, might not be the best approach, they compared the safety and immunogenicity of a double dose of a seasonal vaccine to a booster dose of the vaccine with the standard dose of the same influenza vaccine. Their reasons for choosing these different approaches was because immune responses to standard vaccination in this population are poor, with downstream concerns for risk for influenza disease in both mother and baby. Unfortunately, they did not find that these alternative approaches offered any additional protection. This study had many successes, including showing the ability to engage pregnant women in a novel vaccine study, especially one investigating influenza, which is a vaccine that too few adults feel is needed; a very high uptake of Option B+,2WHOAntiretroviral drugs for treating pregnant women and preventing HIV infection in infants: recommendations for a public health approach. 2010 version. World Health Organization, Geneva2010https://apps.who.int/iris/bitstream/handle/10665/75236/9789241599818_eng.pdf;jsessionid=278CC2640B9AB7FDEE1FCE3EF6F0DED9?sequence=1Referenced9/24/2019Date accessed: November 8, 2019Google Scholar with 95% of women on antiretroviral therapy at the time of study enrolment; and that pregnancy and infant adverse events were similar across the different vaccination groups. They confirmed that no new or unexpected adverse events occurred in any of the vaccination groups, giving physicians some additional encouragement to use this vaccine during pregnancy. Why do I think that they did not find a best vaccine for this population? The issue is complicated by the length and variability of antiretroviral exposure before vaccination and perhaps the corresponding lack of successful virological control. Data from other vaccine studies, while in non-pregnant women, clearly show increased immunological success with virological control,3Abzug MJ Pelton SI Song LY et al.Immunogenicity, safety, and predictors of response after a pneumococcal conjugate and pneumococcal polysaccharide vaccine series in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy.Pediatr Infect Dis J. 2006; 25: 920-929Crossref PubMed Scopus (77) Google Scholar, 4Weinberg A Huang S Fenton T et al.Virologic and immunologic correlates with the magnitude of antibody responses to the hepatitis A vaccine in HIV-infected children on highly active antiretroviral treatment.J Acquir Immune Defic Syndr. 2009; 52: 17-24Crossref PubMed Scopus (16) Google Scholar whereas other studies in pregnant women infected with HIV have shown that lower nadir CD4 count and CD4 percentage, but not virological control (which could not be assessed because too few enrolled with good virological control), might have a role in maternal immune response.5Abzug MJ Nachman SA Muresan P et al.Safety and immunogenicity of 2009 pH1N1 vaccination in HIV-infected pregnant women.Clin Infect Dis. 2013; 56: 1488-1497Crossref PubMed Scopus (25) Google Scholar What is not yet asked or answered, in this study or in the medical community, is where do we go next? If the double-dosed vaccine and the prime boost approaches did not work, the next step would be to look for a better vaccine candidate. This better vaccine might contain a better adjuvant or, in the case of influenza, a better antigen, avoiding the potential mismatch of circulating influenza strains. However, better adjuvants and better antigens are two separate issues that will need to be addressed in parallel if we want protection in this population from influenza via vaccination to be successful. Many novel adjuvants are being evaluated and include products focused on novel mechanisms of action or targets.6Bonam SR Partidos CD Halmuthur SKM Muller S An overview of novel adjuvants designed for improving vaccine efficacy.Trends Pharmacol Sci. 2017; 38: 771-793Summary Full Text Full Text PDF PubMed Scopus (105) Google Scholar Other researchers are approaching the problem differently, targeting conserved viral proteins or protein regions shared among seasonal and pre-pandemic strains.7Sautto GA Kirchenbaum GA Ross TM Towards a universal influenza vaccine: different approaches for one goal.Virol J. 2018; 15: 17Crossref PubMed Scopus (92) Google Scholar The Article by Nunes and colleagues shows that both patients and Institutional Review Boards are in sync with engaging pregnant women in clinical trials and that the idea that the development of studies for pregnant women should be avoided is not acceptable. Unfortunately, far too often, pharmaceutical companies are risk averse with regards to developing pre-licensure studies in pregnant women, relying on post-licensure phase 4 studies, for assessing products in this population. This type of thinking has allowed long delays in bringing and understanding how to use lifesaving treatments in pregnant women, whether they are infected with HIV or not. This risk avoidance approach has resulted in the licensure of only one antiretroviral drug, zidovudine, approved for specific use during pregnancy (compared with other antiretrovirals that have general approval for all adults, but lack specific data in pregnancy), and only vaccines for diphtheria, tetanus, influenza, and hepatitis B with specific approval in pregnancy. Pregnancy is a time of immune compromise and the prevention of illness should be at the forefront of care. The lack of understanding in how to use products, both in the pipeline and those licensed but with no data for use in pregnancy, handicaps our ability to provide optimal care to our pregnant patients and their infants. We should aim to protect pregnant women through research rather than from research and Nunes and colleagues should be commended for trying to do so. I declare no competing interests. I thank Nahida Chakhtoura and Rohan Hazra for valuable discussion and input Immunogenicity and safety of different dosing schedules of trivalent inactivated influenza vaccine in pregnant women with HIV: a randomised controlled trialA regimen of double-dose inactivated influenza vaccine gave slightly greater immunogenicity than did a single-dose regimen in pregnant women living with HIV. However, immunogenicity in the double-dose group was still lower than historical data from the same setting in pregnant women without HIV. More immunogenic vaccines are needed for pregnant women living with HIV to enhance transplacental transfer of vaccine-induced protective antibodies to their newborn infants. Full-Text PDF Open Access